Affinage

TTF1

Transcription termination factor 1 · UniProt Q15361

Length
905 aa
Mass
103.1 kDa
Annotated
2026-04-28
100 papers in source corpus 24 papers cited in narrative 24 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TTF-1 (NKX2-1) is a homeodomain transcription factor that serves as a master regulator of tissue-specific gene expression in the thyroid, lung, and hypothalamus, coordinating differentiation, surfactant homeostasis, neuroendocrine function, and cell proliferation. It binds DNA as a monomer with high sequence specificity and activates thyroglobulin, thyroperoxidase, surfactant protein (SP-A, SP-B, SP-C), RET, PACAP, LHRH, erbB-2, Claudin-6, MYBPH, and α5 nAChR promoters while repressing preproenkephalin and COX-2 transcription (PMID:1811929, PMID:12122016, PMID:11161473, PMID:22174936, PMID:22085929, PMID:15548547). Its transcriptional output is positively regulated by PKA-dependent phosphorylation and acetylation via CBP/p300 and SRC-1, and by co-activators TAZ and PARP-1/PARP-2, whereas ERK-mediated phosphorylation downstream of Ras/Raf signaling and RET/PTC1 oncogene activity repress TTF-1 function post-translationally (PMID:11713256, PMID:14970209, PMID:16461352, PMID:10733581, PMID:9438393). Neuron-specific deletion in mice causes delayed puberty and reduced reproductive capacity without gross morphological defects, establishing a post-morphogenic role in hypothalamic control of female reproduction (PMID:17182767).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1991 High

    Establishing TTF-1 as a tissue-restricted transcription factor: prior to this work, the gene targets and expression domains of TTF-1 were unknown; this study showed it activates thyroglobulin and thyroperoxidase promoters and is expressed in thyroid, lung, and select brain regions from the earliest stages of organogenesis.

    Evidence In situ hybridization, immunohistochemistry, and promoter-reporter assays in thyroid cell lines

    PMID:1811929

    Open questions at the time
    • Lung and brain target genes not yet identified
    • No loss-of-function evidence for developmental necessity
  2. 1993 High

    Resolving TTF-1's DNA-binding mode: it was unclear whether TTF-1 bound DNA as a dimer like many homeodomain proteins; biophysical analysis demonstrated monomeric binding with ≥1000-fold specificity over non-specific DNA, and later work showed the homeodomain's low conformational stability is critical for binding activity.

    Evidence Quantitative EMSA with salt titration (1993); circular dichroism thermal denaturation and urea unfolding coupled to DNA-binding assays (1994)

    PMID:7957942 PMID:8267599

    Open questions at the time
    • No high-resolution structure of full-length TTF-1 on DNA
    • Contribution of flanking domains to specificity unexplored
  3. 1995 Medium

    Demonstrating a proliferative requirement: TTF-1 had been characterized only as a differentiation factor; antisense knockdown revealed it is also required for TSH- and IGF-I-stimulated thyroid cell proliferation, broadening its role beyond terminal differentiation.

    Evidence Antisense oligonucleotide treatment of FRTL-5 thyroid cells with DNA synthesis and cell counting assays

    PMID:7559458

    Open questions at the time
    • Antisense approach lacks specificity controls of modern RNAi/knockout
    • Downstream proliferative targets not identified
  4. 1998 Medium

    Identifying oncogene-mediated post-translational repression and autoregulation: it was unknown how oncogenic signaling affects TTF-1; RET/PTC1 was shown to inactivate TTF-1 without reducing its protein level, and separately, TTF-1 was found to positively autoregulate its own promoter.

    Evidence Reporter assays with RET/PTC1 overexpression (1998); TTF-1 co-transfection activating its own promoter in HepG2 cells (1998)

    PMID:9438393 PMID:9528987

    Open questions at the time
    • Mechanism of RET/PTC1-mediated inactivation not resolved at phosphorylation/PTM level
    • Autoregulation not confirmed by ChIP in endogenous context
  5. 2000 High

    Mapping the ERK phosphorylation sites that repress TTF-1: the post-translational mechanism by which Ras signaling inhibits TTF-1 was unknown; ERK was shown to directly phosphorylate three serines on TTF-1, with an additional ERK-independent Ras pathway cooperating for near-complete inactivation.

    Evidence In vitro kinase assay, Ser→Ala mutagenesis, MEK inhibitors, and Ras effector-domain mutants in reporter assays

    PMID:10733581

    Open questions at the time
    • Identity of the ERK-independent Ras effector pathway not resolved
    • In vivo phosphorylation stoichiometry unknown
  6. 2001 High

    Defining the co-activator complex and PKA-dependent acetylation switch: it was unclear how cAMP/PKA signaling enhances TTF-1 activity; CBP/p300 and SRC-1 were shown to interact with TTF-1 in lung type II cells, with PKA phosphorylation promoting this interaction and TTF-1 hyperacetylation, thereby boosting SP-A transactivation.

    Evidence GST pull-down, immunodepletion, PKA overexpression, adenoviral E1A competition, and cAMP-induced acetylation assays

    PMID:11713256

    Open questions at the time
    • Specific acetylation sites on TTF-1 not mapped
    • Relative contributions of SRC-1 vs. CBP/p300 not dissected in vivo
  7. 2001 High

    Extending TTF-1 into neuroendocrine gene regulation: it was unknown whether TTF-1 controlled hypothalamic genes; TTF-1 was shown to activate LHRH and erbB-2 promoters and repress preproenkephalin in hypothalamic neurons, with expression peaking before puberty.

    Evidence EMSA, promoter-reporter assays, intracerebroventricular antisense knockdown, ISH, and IHC in rat hypothalamus

    PMID:11161473

    Open questions at the time
    • Direct chromatin occupancy at hypothalamic targets not shown (no ChIP)
    • Mechanism of transcriptional repression not characterized
  8. 2002 High

    Identifying PACAP as a direct TTF-1 target in the hypothalamus: this connected TTF-1 to neuropeptide circuits beyond LHRH, showing binding to six motifs in the PACAP promoter and demonstrating in vivo dependence of PACAP mRNA on TTF-1.

    Evidence EMSA, promoter deletion/mutation reporter analysis, intracerebroventricular antisense knockdown with RNase protection assay

    PMID:12122016

    Open questions at the time
    • No ChIP confirmation of occupancy in vivo
    • Functional consequence of PACAP reduction on puberty not tested
  9. 2004 High

    Recruiting TAZ as a co-activator for lung surfactant gene activation and linking TTF-1 to RET in Hirschsprung disease: TAZ was shown to synergize with TTF-1 on the SP-C promoter via WW domain–N-terminal interaction; separately, TTF-1 was found to directly bind the RET promoter, with HSCR-associated SNPs and a patient TTF-1 mutation compromising this activation.

    Evidence Mammalian two-hybrid, GST pull-down, deletion mapping, reporter assays (TAZ study); EMSA, reporter assay, logistic regression on HSCR SNPs (RET study)

    PMID:14970209 PMID:15548547

    Open questions at the time
    • TAZ interaction not validated by endogenous Co-IP
    • Functional impact of RET promoter regulation on enteric nervous system development not shown in animal model
  10. 2006 High

    Identifying PARP-1/PARP-2 as endogenous TTF-1 partners that selectively enhance SP-B: the co-activator landscape for SP-B was undefined; PARP-2 was found to interact with TTF-1's C-terminal domain and specifically boost SP-B promoter activity, together with PARP-1 and Ku70/Ku80 identified by mass spectrometry.

    Evidence Co-immunoprecipitation from MLE15 cells, mass spectrometry, GST domain mapping, reporter assay

    PMID:16461352

    Open questions at the time
    • Whether PARP enzymatic activity (PARylation) is required for co-activation not tested
    • In vivo relevance in PARP-2 knockout lungs not assessed
  11. 2006 High

    Establishing an in vivo post-morphogenic role of TTF-1 in female reproduction: conditional neuron-specific Ttf1 knockout mice showed delayed puberty and shortened reproductive lifespan without hypothalamic structural defects, proving TTF-1 acts beyond early brain patterning.

    Evidence Conditional neuron-specific Ttf1 knockout mice with reproductive phenotyping and gene expression profiling

    PMID:17182767

    Open questions at the time
    • Specific neuronal subtypes requiring TTF-1 not resolved
    • Direct targets mediating the reproductive phenotype not fully identified
  12. 2008 High

    Demonstrating that the TTF-1 binding element is essential for in vivo lung-specific and hormonally regulated SP-A2 expression: transgenic mice with a mutated TBE showed complete loss of SP-A2 transgene expression and hormonal responsiveness, confirming TTF-1 as a non-redundant in vivo driver of surfactant gene regulation.

    Evidence Transgenic mouse reporter with wild-type vs. TBE-mutant hSP-A2 promoters, fetal lung explant hormone treatment

    PMID:18487360

    Open questions at the time
    • Whether other TTF-1 sites compensate for TBE loss at endogenous locus not tested
    • Chromatin accessibility changes at mutant TBE not examined
  13. 2011 High

    Expanding TTF-1's role to anti-metastatic transcriptional programs and hypothalamic thermoregulation: TTF-1 was shown to directly activate MYBPH transcription (suppressing ROCK1-driven cell motility and metastasis) and to repress COX-2 in hypothalamic non-neuronal cells (controlling body temperature).

    Evidence ChIP on MYBPH promoter, MYBPH–ROCK1 Co-IP, kinase assays, mouse metastasis model (MYBPH study); EMSA, reporter, in vivo antisense KD with temperature measurement (COX-2 study)

    PMID:22085929 PMID:22174936

    Open questions at the time
    • MYBPH-independent anti-metastatic targets of TTF-1 not delineated
    • Molecular mechanism of COX-2 repression (co-repressor identity) not defined
  14. 2011 Medium

    Linking TTF-1 nuclear localization directly to surfactant homeostasis in human disease: cytoplasmic retention of TTF-1 protein in type II pneumocytes was associated with markedly reduced SP-B synthesis and respiratory failure in an infant, functionally connecting nuclear import to transcriptional output.

    Evidence Confocal immunofluorescence of lung biopsy, stable-isotope SP-B kinetic assay, gene sequencing

    PMID:21867529

    Open questions at the time
    • Mechanism causing cytoplasmic retention not identified
    • Single clinical case without genetic rescue or cell-based validation
    • Causative mutation or transport defect not established
  15. 2014 High

    Positioning TTF-1 as the required mediator of mTOR inhibitor-induced thyroid redifferentiation: siRNA knockdown of TTF-1 completely abolished NIS re-expression and iodine uptake induced by mTOR inhibition, establishing TTF-1 downstream of mTOR signaling in thyroid cancer cells.

    Evidence mTOR inhibitor treatment of thyroid carcinoma lines, TTF-1 siRNA epistasis, NIS mRNA/protein and iodine uptake assays

    PMID:24712572

    Open questions at the time
    • Whether mTOR controls TTF-1 protein stability, phosphorylation, or transcription not resolved
    • In vivo relevance for radioiodine therapy not demonstrated

Open questions

Synthesis pass · forward-looking unresolved questions
  • Unresolved: the full genome-wide target repertoire of TTF-1 across its three expression domains (thyroid, lung, brain) has not been systematically defined by ChIP-seq; the structural basis for how post-translational modifications alter TTF-1 conformation and co-activator selectivity remains unknown; and the nuclear import mechanism whose failure causes surfactant disease has not been identified.
  • No genome-wide ChIP-seq across tissue types
  • No full-length TTF-1 crystal or cryo-EM structure
  • Nuclear import pathway and transport signals not characterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 13 GO:0003677 DNA binding 10
Localization
GO:0005634 nucleus 2
Pathway
R-HSA-74160 Gene expression (Transcription) 13 R-HSA-1266738 Developmental Biology 3 R-HSA-162582 Signal Transduction 3
Partners
BRN2CBPFOXA2PARP1PARP2PAX8SRC1TAZ

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1991 TTF-1 (a homeodomain-containing transcription factor) activates thyroglobulin and thyroperoxidase gene promoters in differentiated thyroid cell lines, and its mRNA/protein show clear nuclear localization in thyroid, lung, and restricted brain regions from the earliest stages of organ differentiation. In situ hybridization, immunohistochemistry, promoter activation assays in thyroid cell lines Development High 1811929
2004 TAZ (transcriptional co-activator with PDZ-binding motif) directly interacts with the NH2-terminal domain of TTF-1 via its WW domain, and this interaction synergistically activates surfactant protein-C (SP-C) promoter transcription in lung epithelial cells. Mammalian two-hybrid assay, GST pull-down, co-transfection luciferase reporter assay, deletion analysis The Journal of biological chemistry High 14970209
2001 CBP/p300 and SRC-1 interact with TTF-1 in vitro and in lung type II cell nuclear extracts; PKA-mediated phosphorylation of TTF-1 facilitates this interaction and leads to TTF-1 hyperacetylation, enhancing its DNA-binding and transcriptional activation of the SP-A promoter. In vitro GST pull-down, SRC-1 immunodepletion from nuclear extracts, transient transfection reporter assay, PKA catalytic subunit overexpression, adenoviral E1A competition, cAMP-induced acetylation assay The Journal of biological chemistry High 11713256
2000 ERK directly phosphorylates TTF-1 at three serine residues (identified by in vitro kinase assay and alanine mutagenesis), and the Ras/Raf/MEK/ERK pathway represses TTF-1 transcriptional activity; an additional ERK-independent Ras pathway (via V12N38 Ras) cooperates to produce near-complete loss of TTF-1 function. In vitro kinase assay, site-directed mutagenesis (Ser→Ala), MEK inhibitors (U0126/PD98059), transient transfection reporter assay, Ras effector-region mutants Molecular and cellular biology High 10733581
2006 PARP-2 (and PARP-1/Ku70/Ku80) co-immunoprecipitate with endogenous TTF-1 in lung epithelial cells; the E domain of PARP-2 interacts with the C-terminal domain of TTF-1; PARP-1 and PARP-2 selectively enhance surfactant protein-B (SP-B) promoter activity when co-expressed with TTF-1. Co-immunoprecipitation from MLE15 cell extracts, mass spectrometry identification, GST domain-mapping pull-down, transient transfection reporter assay The Journal of biological chemistry High 16461352
1998 RET/PTC1 oncogene expression leaves TTF-1 protein levels unchanged but renders TTF-1 transcriptionally inactive (assayed on a synthetic TTF-1-target promoter), indicating posttranslational inactivation of TTF-1 function downstream of RET/PTC1 signaling. Transient transfection reporter assay using synthetic TTF-1 target promoter, Western blot, adoptive overexpression Cell growth & differentiation Medium 9438393
2004 TTF-1 binds to a specific site in the RET promoter; HSCR-associated RET promoter SNPs that overlap the TTF-1 binding site decrease TTF-1-activated RET transcription; a patient-derived TTF-1 missense mutation (Gly322Ser) compromises transactivation of HSCR-associated RET promoter haplotypes. Luciferase reporter assay, electrophoretic mobility shift assay (EMSA), weighted logistic regression on SNP data, functional mutation analysis Human molecular genetics High 15548547
2001 TTF-1 binds to and transactivates the erbB-2 and LHRH gene promoters in hypothalamic neurons, while repressing transcription of the preproenkephalin gene; hypothalamic TTF-1 expression increases transiently prior to puberty onset, suggesting a role in the transcriptional control of female sexual development. Electrophoretic mobility shift assay (DNA binding), promoter-reporter transactivation assay, intracerebroventricular antisense oligonucleotide knockdown, in situ hybridization, immunohistochemistry Molecular and cellular neurosciences High 11161473
2006 Neuron-specific deletion of Ttf1 in mice causes delayed puberty, reduced reproductive capacity, and a short reproductive span without basal ganglia/hypothalamic morphological defects, demonstrating a post-morphogenic role of TTF-1 in hypothalamic neuroendocrine control of female reproduction. Conditional neuron-specific Ttf1 knockout mice, gene expression profiling, behavioral/reproductive phenotyping The Journal of neuroscience High 17182767
2002 TTF-1 activates PACAP gene transcription by binding to six of seven conserved TTF-1-binding motifs in the PACAP 5'-flanking region; deletion of the core motif at -369 abolishes transactivation; intracerebroventricular antisense TTF-1 oligonucleotide knockdown significantly decreases hypothalamic PACAP mRNA. EMSA (TTF-1 homeodomain binding to PACAP promoter sites), promoter-reporter deletion/mutational analysis, intracerebroventricular antisense KD with RNase protection assay The Journal of biological chemistry High 12122016
2011 MYBPH is a transcriptional target of TTF-1; TTF-1 drives MYBPH expression and MYBPH inhibits ROCK1 through direct physical interaction, thereby suppressing myosin regulatory light chain phosphorylation and LIMK activation, reducing actomyosin-driven single-cell motility and cancer metastasis. Chromatin immunoprecipitation (TTF-1 on MYBPH promoter), co-immunoprecipitation (MYBPH–ROCK1), in vitro kinase assays, shRNA knockdown, cell motility assays, mouse metastasis models The EMBO journal High 22085929
1994 The isolated TTF-1 homeodomain (TTF-1HD) binds DNA as a monomer; its conformational stability is low (Tm 42°C, ΔG ~1.4 kcal/mol) and helical flexibility is important for DNA-binding activity, as small reductions in α-helical content significantly diminish DNA binding. Circular dichroism thermal denaturation, isothermal urea unfolding, DNA-binding assays FEBS letters High 7957942
1993 The TTF-1 homeodomain (TTF-1HD) exists as a monomer in solution and binds DNA as a monomer; at physiological salt conditions, its affinity for specific DNA sequences is at least 1000-fold higher than for non-specific sequences. Biochemical DNA-binding assays with titration of KCl concentration, gel-shift (EMSA) Biochemical and biophysical research communications High 8267599
1998 The TTF-1/T/EBP gene is autoregulated: the TTF-1 promoter contains ~24 putative TTF-1 binding sites, and co-transfection of a TTF-1 expression vector activates its own promoter reporter in HepG2 cells that lack endogenous TTF-1; multiple promoters and alternative splicing generate a family of TTF-1 mRNAs. Cotransfection reporter assay, RNase protection assay, Northern blot, cDNA cloning/sequencing Endocrinology Medium 9528987
2009 Three TTF-1/NKX2-1 missense mutations (L176V, P202L, Q210P) cause loss of transactivation capacity on the human thyroglobulin enhancer/promoter; deficient activity of P202L is completely rescued by cotransfected wild-type PAX8, whereas L176V and Q210P abolish the PAX8 synergism. Transient transfection transactivation assay on thyroglobulin enhancer/promoter reporter, cotransfection with PAX8 Human molecular genetics High 19336474
1995 Antisense oligonucleotide-mediated blockade of TTF-1 in FRTL-5 thyroid cells reduces TSH- and IGF-I-stimulated cell proliferation (DNA synthesis and cell counting) by ~65%, demonstrating that TTF-1 expression is required for thyroid cell proliferation via the cAMP pathway. Antisense oligonucleotide treatment, DNA synthesis assay, cell counting The Journal of biological chemistry Medium 7559458
2011 TTF-1 transactivates the α5 nicotinic acetylcholine receptor (nAChR) subunit promoter by binding specific TTF-1 response elements; site-directed mutagenesis of these elements abolishes TTF-1-driven α5 transcription in proximal and distal lung epithelial cell lines. Promoter-reporter assay, site-directed mutagenesis of TTF-1 response elements, exogenous TTF-1 overexpression Respiratory research Medium 21143907
2008 In the TTF-1 proximal promoter, ZBP-89, Sp1/Sp3, and TTF-1 itself bind functional sites identified by EMSA and ChIP; TNF-α inhibits TTF-1 gene transcription and promoter activity, suppressing TTF-1 binding to its own promoter while increasing threonine phosphorylation of Sp1, without altering Sp1 or HNF-3 protein levels. Promoter deletion analysis, EMSA, chromatin immunoprecipitation (ChIP), mutational analysis, TNF-α treatment of H441 and primary alveolar type II cells American journal of physiology. Lung cellular and molecular physiology High 21784970
2011 TTF-1 inhibits COX-2 gene transcription in hypothalamic astrocytes and endothelial cells by binding to specific sites in the COX-2 promoter; intracerebroventricular antisense TTF-1 knockdown increases COX-2 synthesis in non-neuronal hypothalamic cells and causes hyperthermia. EMSA (TTF-1 binding to COX-2 promoter sites), promoter-reporter assay, intracerebroventricular antisense oligonucleotide knockdown, double immunohistochemistry, body temperature measurement PloS one High 22174936
2014 TTF-1 and its co-regulators FoxA2 and Gata-6 transcriptionally activate the Claudin-6 (Cldn6) promoter in both proximal airway (Beas2B) and distal alveolar (A-549) epithelial cell lines, demonstrating that Cldn6 is a direct transcriptional target of TTF-1 during lung organogenesis. Promoter-reporter assay (0.5, 1.0, 2.0-kb Cldn6 promoter fragments co-transfected with TTF-1 expression vectors), immunofluorescence co-localization Respiratory research Medium 24970044
2008 The TTF-1 response element (TBE at -171 bp) in the hSP-A2 promoter is essential for lung cell-specific, developmental, and hormonal (cAMP/IL-1/dexamethasone) regulation of SP-A2 expression in vivo, demonstrated in transgenic mice where TBE mutation abolishes detectable transgene expression and hormonal responsiveness in fetal lung. Transgenic mouse reporter assay (hSP-A2-hGH reporter with wild-type or TBE-mutant promoters), cultured fetal lung explant hormone treatment American journal of physiology. Lung cellular and molecular physiology High 18487360
2013 BRN2, a neural lineage-specific homeoprotein, directly binds the TTF-1 isoform 2 promoter (confirmed by ChIP) and substantially upregulates TTF-1 expression in small-cell lung cancer (SCLC) cells; BRN2 knockdown considerably downregulates TTF-1 in SCLC, whereas FOXA1/2 weakly activate the TTF-1 promoter. TTF-1 promoter reporter assay, chromatin immunoprecipitation (ChIP), siRNA knockdown of BRN2, transfection of expression vectors (BRN2, FOXA1/2, LHX2/6) Laboratory investigation High 23358112
2014 mTOR inhibition promotes TTF-1-dependent redifferentiation of thyroid carcinoma cells: siRNA knockdown of TTF-1 completely abrogates mTOR inhibitor-induced sodium-iodide symporter (NIS) expression and increased iodine uptake, placing TTF-1 as a required transcriptional mediator of mTOR-controlled thyroid redifferentiation. mTOR inhibitor treatment of thyroid carcinoma cell lines (BC-PAP, FTC133, TPC1), siRNA knockdown of TTF-1, NIS mRNA/protein assay, iodine uptake assay The Journal of clinical endocrinology and metabolism High 24712572
2011 Defective nuclear targeting of TTF-1 protein (TTF-1 retained in cytoplasm of type II cells rather than nucleus) is associated with markedly reduced surfactant protein-B synthesis and disrupted surfactant homeostasis in an infant with recurrent respiratory failure, functionally linking TTF-1 nuclear localization to SP-B transcription. Confocal immunofluorescence microscopy of lung biopsy, SP-B kinetic stable-isotope synthesis assay, ABCA3/SFTPB/NKX2.1 gene sequencing Respiratory research Medium 21867529

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1991 The transcription factor TTF-1 is expressed at the onset of thyroid and lung morphogenesis and in restricted regions of the foetal brain. Development (Cambridge, England) 788 1811929
2002 TTF-1 expression in pulmonary adenocarcinomas. The American journal of surgical pathology 296 12023581
1994 Expression of thyroid-specific transcription factors TTF-1 and PAX-8 in human thyroid neoplasms. Cancer research 222 8062273
2009 Five new TTF1/NKX2.1 mutations in brain-lung-thyroid syndrome: rescue by PAX8 synergism in one case. Human molecular genetics 150 19336474
2004 TAZ interacts with TTF-1 and regulates expression of surfactant protein-C. The Journal of biological chemistry 150 14970209
2003 p63 and TTF-1 immunostaining. A useful marker panel for distinguishing small cell carcinoma of lung from poorly differentiated squamous cell carcinoma of lung. American journal of clinical pathology 122 12760288
2017 SMARCA4-deficient pulmonary adenocarcinoma: clinicopathological, immunohistochemical, and molecular characteristics of a novel aggressive neoplasm with a consistent TTF1neg/CK7pos/HepPar-1pos immunophenotype. Virchows Archiv : an international journal of pathology 116 28555282
2010 An immunohistochemical study of cervical neuroendocrine carcinomas: Neoplasms that are commonly TTF1 positive and which may express CK20 and P63. The American journal of surgical pathology 98 20182342
2004 The role of TTF-1 in differentiating primary and metastatic lung adenocarcinomas. Pathology oncology research : POR 98 15188024
2001 TTF-1, a homeodomain gene required for diencephalic morphogenesis, is postnatally expressed in the neuroendocrine brain in a developmentally regulated and cell-specific fashion. Molecular and cellular neurosciences 97 11161473
2011 Combination of napsin A and TTF-1 immunohistochemistry helps in differentiating primary lung adenocarcinoma from metastatic carcinoma in the lung. Applied immunohistochemistry & molecular morphology : AIMM 96 21464700
2005 Usefulness of CDX2 and TTF-1 in differentiating gastrointestinal from pulmonary carcinoids. American journal of clinical pathology 87 15716236
2005 Alternative epithelial markers in sarcomatoid carcinomas of the head and neck, lung, and bladder-p63, MOC-31, and TTF-1. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 86 15976812
2000 Expression of thyroid transcription factor-1 (TTF-1) in human C cells and medullary thyroid carcinomas. Human pathology 75 10746684
2011 MYBPH, a transcriptional target of TTF-1, inhibits ROCK1, and reduces cell motility and metastasis. The EMBO journal 74 22085929
2004 TTF-1 and RET promoter SNPs: regulation of RET transcription in Hirschsprung's disease. Human molecular genetics 74 15548547
2012 PDX-1, CDX-2, TTF-1, and CK7: a reliable immunohistochemical panel for pancreatic neuroendocrine neoplasms. The American journal of surgical pathology 72 22498824
2006 TTF-1 and p63 for distinguishing pulmonary small-cell carcinoma from poorly differentiated squamous cell carcinoma in previously pap-stained cytologic material. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 72 16680154
2004 Histopathologic classification of lung cancer: Relevance of cytokeratin and TTF-1 immunophenotyping. Annals of diagnostic pathology 67 15494931
2001 Role of CBP/p300 and SRC-1 in transcriptional regulation of the pulmonary surfactant protein-A (SP-A) gene by thyroid transcription factor-1 (TTF-1). The Journal of biological chemistry 67 11713256
2013 A mutation in TTF1/NKX2.1 is associated with familial neuroendocrine cell hyperplasia of infancy. Chest 65 23787483
2011 TTF-1 and Napsin A double stain: a useful marker for diagnosing lung adenocarcinoma on fine-needle aspiration cell blocks. Cancer cytopathology 65 21287692
2015 An Integrated Molecular Analysis of Lung Adenocarcinomas Identifies Potential Therapeutic Targets among TTF1-Negative Tumors, Including DNA Repair Proteins and Nrf2. Clinical cancer research : an official journal of the American Association for Cancer Research 56 25878335
2014 The utility of a novel triple marker (combination of TTF1, napsin A, and p40) in the subclassification of non-small cell lung cancer. Human pathology 55 24746197
2000 Multiple ras downstream pathways mediate functional repression of the homeobox gene product TTF-1. Molecular and cellular biology 54 10733581
2010 TTF1 expression in normal lung neuroendocrine cells and related tumors: immunohistochemical study comparing two different monoclonal antibodies. Virchows Archiv : an international journal of pathology 53 20694477
1998 Expression of the RET/PTC1 oncogene impairs the activity of TTF-1 and Pax-8 thyroid transcription factors. Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research 51 9438393
2006 PARP-2 interacts with TTF-1 and regulates expression of surfactant protein-B. The Journal of biological chemistry 49 16461352
1998 Multiple transcripts encoded by the thyroid-specific enhancer-binding protein (T/EBP)/thyroid-specific transcription factor-1 (TTF-1) gene: evidence of autoregulation. Endocrinology 49 9528987
2011 Diagnostic utility of PAX8, TTF-1 and napsin A for discriminating metastatic carcinoma from primary adenocarcinoma of the lung. Biotechnic & histochemistry : official publication of the Biological Stain Commission 48 21838611
2006 Deletion of the Ttf1 gene in differentiated neurons disrupts female reproduction without impairing basal ganglia function. The Journal of neuroscience : the official journal of the Society for Neuroscience 47 17182767
2001 Expression of thyroid transcription factor-1 (TTF-1) gene in the ventral forebrain and endostyle of the agnathan vertebrate, Lampetra japonica. Genesis (New York, N.Y. : 2000) 47 11416863
1995 Function of the homeo and paired domain proteins TTF-1 and Pax-8 in thyroid cell proliferation. The Journal of biological chemistry 47 7559458
1997 Absence of mutations in the gene encoding thyroid transcription factor-1 (TTF-1) in patients with thyroid dysgenesis. Thyroid : official journal of the American Thyroid Association 46 9226206
2014 The relationship between TTF-1 expression and EGFR mutations in lung adenocarcinomas. PloS one 44 24743427
2009 Characterizing the developmental pathways TTF-1, NKX2-8, and PAX9 in lung cancer. Proceedings of the National Academy of Sciences of the United States of America 44 19279207
2013 Update on hypophysitis and TTF-1 expressing sellar region masses. Brain pathology (Zurich, Switzerland) 43 23701182
2007 Biomarker-assisted diagnosis of ovarian, cervical and pulmonary small cell carcinomas: the role of TTF-1, WT-1 and HPV analysis. Histopathology 43 17727473
2008 If it's not CK5/6 positive, TTF-1 negative it's not a squamous cell carcinoma of lung. APMIS : acta pathologica, microbiologica, et immunologica Scandinavica 39 18754327
2007 WT1, monoclonal CEA, TTF1, and CA125 antibodies in the differential diagnosis of lung, breast, and ovarian adenocarcinomas in serous effusions. Diagnostic cytopathology 39 17497661
2008 Induction of sodium iodide symporter gene and molecular characterisation of HNF3 beta/FoxA2, TTF-1 and C/EBP beta in thyroid carcinoma cells. British journal of cancer 38 18682709
2014 mTOR Inhibition promotes TTF1-dependent redifferentiation and restores iodine uptake in thyroid carcinoma cell lines. The Journal of clinical endocrinology and metabolism 37 24712572
2009 Cutaneous metastasis from large-cell neuroendocrine carcinoma of the urinary bladder expressing CK20 and TTF-1. The American Journal of dermatopathology 31 19318803
2003 Developmental cooperation of leukemia inhibitory factor and insulin-like growth factor I in mice is tissue-specific and essential for lung maturation involving the transcription factors Sp3 and TTF-1. Mechanisms of development 31 12591604
2016 Induction of TTF-1 or PAX-8 expression on proliferation and tumorigenicity in thyroid carcinomas. International journal of oncology 30 27573549
2009 GCDFP-15 positive and TTF-1 negative primary lung neoplasms: a tissue microarray study of 381 primary lung tumors. Applied immunohistochemistry & molecular morphology : AIMM 28 19620839
2013 Neural lineage-specific homeoprotein BRN2 is directly involved in TTF1 expression in small-cell lung cancer. Laboratory investigation; a journal of technical methods and pathology 27 23358112
2017 TTF-1- and/or CD56-positive Circulating Tumor Cells in patients with small cell lung cancer (SCLC). Scientific reports 26 28349943
2014 Developmental lung expression and transcriptional regulation of claudin-6 by TTF-1, Gata-6, and FoxA2. Respiratory research 25 24970044
2013 TTF-1 expression in breast carcinoma: an unusual but real phenomenon. Histopathology 25 24111789
2008 Transcription expression and clinical significance of TTF-1 mRNA in pleural effusion of patients with lung cancer. Diagnostic cytopathology 25 18855882
2019 Value of SATB2, ISL1, and TTF1 to differentiate rectal from other gastrointestinal and lung well-differentiated neuroendocrine tumors. Pathology, research and practice 23 31133441
2017 Pituicytoma: Review of commonalities and distinguishing features among TTF-1 positive tumors of the central nervous system. Annals of diagnostic pathology 23 28807344
2015 The expression of TTF-1 and Napsin A in early-stage lung adenocarcinoma correlates with the results of surgical treatment. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 22 25982999
2002 Regulation of pituitary adenylate cyclase-activating polypeptide gene transcription by TTF-1, a homeodomain-containing transcription factor. The Journal of biological chemistry 22 12122016
1994 Analysis of the conformation and stability of rat TTF-1 homeodomain by circular dichroism. FEBS letters 22 7957942
2015 The diagnostic utility of the triple markers Napsin A, TTF-1, and PAX8 in differentiating between primary and metastatic lung carcinomas. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 21 26427663
2016 Utility of TTF-1 and Napsin-A in the work-up of malignant effusions. Diagnostic cytopathology 20 26799356
2014 ΔNp63, CK5/6, TTF-1 and napsin A, a reliable panel to subtype non-small cell lung cancer in biopsy specimens. International journal of clinical and experimental pathology 20 25120805
2011 Thyroid transcription factor-1 (TTF-1) gene: identification of ZBP-89, Sp1, and TTF-1 sites in the promoter and regulation by TNF-α in lung epithelial cells. American journal of physiology. Lung cellular and molecular physiology 20 21784970
2009 TTF-1 expression in nephroblastoma. The American journal of surgical pathology 20 19011567
2022 Non-small cell lung carcinomas with diffuse coexpression of TTF1 and p40: clinicopathological and genomic features of 14 rare biphenotypic tumours. Histopathology 19 36130728
2012 Dual color multiplex TTF-1 + Napsin A and p63 + CK5 immunostaining for subcategorizing of poorly differentiated pulmonary non-small carcinomas into adenocarcinoma and squamous cell carcinoma in fine needle aspiration specimens. CytoJournal 19 22582081
2022 Association of thyroid transcription factor-1 (TTF-1) expression with efficacy of PD-1/PD-L1 inhibitors plus pemetrexed and platinum chemotherapy in advanced non-squamous non-small cell lung cancer. Translational lung cancer research 18 36519019
2018 The expression of TTF1, CDX2 and ISL1 in 74 poorly differentiated neuroendocrine carcinomas. Annals of diagnostic pathology 18 30236546
2016 TTF-1 and PAX5 Are Frequently Expressed in Combined Merkel Cell Carcinoma. The American Journal of dermatopathology 17 27322785
2008 EGFR, TTF-1 and Mdm2 expression in stage III non-small cell lung cancer: a positive association. Lung cancer (Amsterdam, Netherlands) 17 18355939
2023 TTF-1 Expression and Clinical Outcomes of Combined Chemoimmunotherapy in Patients With Advanced Lung Adenocarcinoma: A Prospective Observational Study. JTO clinical and research reports 16 37020925
2021 Coexpression of ΔNp63/p40 and TTF1 Within Most of the Same Individual Cells Identifies Life-Threatening NSCLC Featuring Squamous and Glandular Biphenotypic Differentiation: Clinicopathologic Correlations. JTO clinical and research reports 16 34746884
2020 TTF-1 Positive Primary Small Cell Carcinoma of the Breast: A Case Report and Review of the Literature. Frontiers in endocrinology 16 32411090
2011 Altered surfactant homeostasis and recurrent respiratory failure secondary to TTF-1 nuclear targeting defect. Respiratory research 16 21867529
2008 TTF-1 response element is critical for temporal and spatial regulation and necessary for hormonal regulation of human surfactant protein-A2 promoter activity. American journal of physiology. Lung cellular and molecular physiology 16 18487360
2021 NKX2.1 (TTF1) germline mutation associated with pulmonary fibrosis and lung cancer. ERJ open research 15 34760996
2019 When tumor doesn't read textbook. Third case of TTF1 and p40 co-expression in the same tumour cells in a non-small cell carcinoma. A potential new entity to consider? Pathologica 15 31388196
2019 Application of GATA 3 and TTF-1 in differentiating parathyroid and thyroid nodules on cytology specimens. Diagnostic cytopathology 15 31713988
2018 Positivity for GATA3 and TTF-1 (SPT24), and Negativity for Monoclonal PAX8 Expand the Biomarker Profile of the Solid Cell Nests of the Thyroid Gland. Endocrine pathology 15 29313264
2018 TTF-1 Expression Predicts the Merit of Additional Antiangiogenic Treatment in Non-squamous Non-small Cell Lung Cancer. Anticancer research 15 30194207
2015 Co-expression of TTF-1 and neuroendocrine markers in the human fetal lung and pulmonary neuroendocrine tumors. Acta histochemica 14 25722034
2015 TTF-1 and napsin A on cell blocks and supernatants of pleural fluids for labeling malignant effusions. Respirology (Carlton, Vic.) 13 25873201
2012 IMP3, NESP55, TTF-1 and CDX2 serve as an immunohistochemical panel in the distinction among small-cell carcinoma, gastrointestinal carcinoid, and pancreatic endocrine tumor metastasized to the liver. Applied immunohistochemistry & molecular morphology : AIMM 13 22495359
2010 TTF-1 regulates α5 nicotinic acetylcholine receptor (nAChR) subunits in proximal and distal lung epithelium. Respiratory research 13 21143907
2005 Aberrant expression of TTF-1 and forkhead factor HFH-4 in atrophic gastritis and ciliated metaplasia suggests gastric broncho-pulmonary transdetermination. The Journal of pathology 13 15912575
2003 Pulmonary well-differentiated fetal adenocarcinoma expressing lineage-specific transcription factors (TTF-1 and GATA-6) to respiratory epithelial differentiation: an immunohistochemical and ultrastructural study. Virchows Archiv : an international journal of pathology 13 12684771
2024 TTF-1 is a highly sensitive but not fully specific marker for pulmonary and thyroidal cancer: a tissue microarray study evaluating more than 17,000 tumors from 152 different tumor entities. Virchows Archiv : an international journal of pathology 12 39377914
2021 SMARCA4 (BRG1) and SMARCB1 (INI1) expression in TTF-1 negative neuroendocrine carcinomas including merkel cell carcinoma. Pathology, research and practice 12 33581550
2021 An algorithmic approach utilizing CK7, TTF1, beta-catenin, CDX2, and SSTR2A can help differentiate between gastrointestinal and pulmonary neuroendocrine carcinomas. Virchows Archiv : an international journal of pathology 12 33733343
2020 The Incidence of Labelling of Non-Lung Adenocarcinomas With Antibodies Against TTF-1 and Diagnostic Implications. Applied immunohistochemistry & molecular morphology : AIMM 12 31135446
2017 Expressions and significances of TTF-1 and PTEN in early endometrial cancer. European review for medical and pharmacological sciences 12 28745797
2011 Inhibition of tumor angiogenesis by TTF1 from extract of herbal medicine. World journal of gastroenterology 12 22171128
2007 Mutational analysis of thyroid transcription factor-1 gene (TTF-1) in lung carcinomas. In vitro cellular & developmental biology. Animal 12 18071837
2021 Correlation of TTF-1 immunoexpression and EGFR mutation spectrum in non-small cell lung carcinoma. Journal of pathology and translational medicine 11 34233113
2018 Immunohistochemical and Biochemical Expression Patterns of TTF-1, RAGE, GLUT-1 and SOX2 in HCV-Associated Hepatocellular Carcinomas. Asian Pacific journal of cancer prevention : APJCP 11 29373917
2011 TTF1-induced apoptosis of HepG-2 cells through a mitochondrial pathway. Oncology reports 11 21637920
2008 The value of immunohistochemical expression of TTF-1, CK7 and CK20 in the diagnosis of primary and secondary lung carcinomas. Saudi medical journal 11 18626520
1993 Effect of salt concentration on TTF-1 HD binding to specific and non-specific DNA sequences. Biochemical and biophysical research communications 11 8267599
2019 The utility of TTF-1, napsin A, CK5 and p63 staining in the sub-classification of non-small cell carcinoma of the lung. Cytopathology : official journal of the British Society for Clinical Cytology 10 31206846
2019 REG4 is an indicator for KRAS mutant lung adenocarcinoma with TTF-1 low expression. Journal of cancer research and clinical oncology 10 31428934
2018 TTF1 Expression in Pulmonary Metastatic Rectal Adenocarcinoma. Case reports in gastrointestinal medicine 10 30631609
2011 TTF-1 action on the transcriptional regulation of cyclooxygenase-2 gene in the rat brain. PloS one 10 22174936
2020 CDX2, SATB2, GATA3, TTF1, and PAX8 Immunohistochemistry in Krukenberg Tumors. International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists 9 32045390