Affinage

FGF3

Fibroblast growth factor 3 · UniProt P11487

Length
239 aa
Mass
26.9 kDa
Annotated
2026-04-28
100 papers in source corpus 36 papers cited in narrative 32 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

FGF3 is a heparin-binding secreted growth factor of the fibroblast growth factor family that functions as a key paracrine/autocrine signal in embryonic patterning, organogenesis, and epithelial proliferation. A single CUG-initiated translation product is partitioned between secretion (via signal peptide cleavage) and nuclear localization (via a bipartite NLS), and the secreted glycoprotein preferentially activates FGFR2-IIIb to drive MAPK/ERK signaling (PMID:8076608, PMID:8622866). FGF3 acts redundantly with FGF8 and FGF10 to induce otic placode formation and inner ear morphogenesis, patterns hindbrain segmental identity through an r4 signaling center activating the Pea3→Krox20 cascade, specifies adenohypophyseal progenitors from the ventral diencephalon, and promotes epibranchial placode neurogenesis, while its transcription is positively regulated by SOX7/GATA-4 and repressed by a SOX6–CtBP2 complex (PMID:11437442, PMID:12810586, PMID:15229178, PMID:16077091, PMID:20553903, PMID:11504872, PMID:15082719). Homozygous loss-of-function FGF3 mutations in humans cause LAMM syndrome (labyrinthine aplasia, microtia, and microdontia), confirming its essential role in inner ear and craniofacial development (PMID:18435799).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 1986 High

    Establishing FGF3 as a member of the FGF family resolved the identity of the int-2 proto-oncogene product, showing it encodes a ~27 kDa protein with FGF homology organized across at least three exons, with four mRNA classes from alternate start/polyadenylation sites.

    Evidence cDNA sequencing, Northern blot, primer extension, RNase protection in mouse

    PMID:2841106 PMID:3013624 PMID:3416832

    Open questions at the time
    • No receptor specificity determined
    • No functional activity demonstrated at this stage
  2. 1989 High

    Demonstrating that FGF3 protein has mesoderm-inducing and mitogenic activity established it as a functional growth factor, not merely an oncogene-associated sequence.

    Evidence Xenopus animal cap mesoderm induction assay and mammalian fibroblast DNA synthesis assay

    PMID:2483371

    Open questions at the time
    • Receptor identity unknown
    • In vivo developmental role not yet tested
  3. 1990 High

    Transgenic overexpression causing mammary and prostatic epithelial hyperplasia demonstrated that FGF3 acts as a potent epithelial growth factor in vivo, linking it to oncogenic potential in specific tissues.

    Evidence MMTV-driven FGF3 transgenic mice with histological analysis

    PMID:1690126

    Open questions at the time
    • Mechanism of autocrine vs. paracrine action unclear
    • Receptor specificity in mammary tissue unknown
  4. 1992 Medium

    Transplantation studies and Wnt-1/FGF3 bitransgenic analysis established that FGF3 acts as an autocrine/ultra-short-range paracrine factor in mammary epithelium and cooperates with Wnt-1 in mammary tumorigenesis through complementary pathways.

    Evidence Transgenic mammary tissue transplantation; doubly transgenic Wnt-1/int-2 mice with tumor incidence analysis

    PMID:1317463 PMID:1530875

    Open questions at the time
    • Molecular basis of Wnt-1 and FGF3 pathway complementation not defined
    • Identity of cooperating downstream effectors unknown
  5. 1993 High

    Two landmark discoveries — Fgf3 knockout mice showing tail and inner ear defects, and biochemical characterization of secreted glycosylated FGF3 forms binding heparin and activating FGFR1/2 — jointly established FGF3 as a heparin-binding FGFR ligand required for otic vesicle morphogenesis and tail bud development.

    Evidence Targeted gene disruption in mouse; COS-1 cell expression with heparin-Sepharose binding, glycosylation analysis, and FGFR-dependent mitogenicity assays

    PMID:8223243 PMID:8223431

    Open questions at the time
    • Specific FGFR isoform preference not yet resolved
    • Redundancy with other FGFs in ear development not addressed
  6. 1994 High

    Demonstrating that a single CUG-initiated FGF3 translation product is partitioned between secretory and nuclear fates by competing signal peptide and bipartite NLS resolved the long-standing question of how one mRNA generates two functionally distinct protein pools.

    Evidence In vitro translation, COS-1 transfection, deletion/replacement mutagenesis, heterologous fusion proteins

    PMID:8076608

    Open questions at the time
    • Functional role of nuclear FGF3 undefined
    • Regulatory mechanism controlling secretory vs. nuclear partitioning in vivo unknown
  7. 1996 High

    Receptor binding studies with zebrafish/Xenopus FGF3 chimeras established preferential binding to FGFR2-IIIb over IIIc, with C-terminal sequences determining receptor affinity, mitogenic potency, and transforming activity.

    Evidence COS-1 transfection, competition receptor binding assay, chimeric protein analysis

    PMID:8622866

    Open questions at the time
    • Crystal structure of FGF3–FGFR2 complex unavailable
    • Whether FGFR2-IIIb preference holds in all vertebrate orthologs untested
  8. 2001 High

    Identification of SOX6–CtBP2 as a transcriptional repressor complex at the Fgf3 promoter, with mutually exclusive SOX6/FGF3 expression in the otic vesicle, established the first direct transcriptional regulatory mechanism for FGF3.

    Evidence Yeast one-hybrid/two-hybrid, reporter gene assay, mutagenesis, in situ hybridization

    PMID:11504872

    Open questions at the time
    • Whether SOX6–CtBP2 repression operates in tissues other than otic vesicle unknown
    • Chromatin-level mechanism not characterized
  9. 2001 High

    Morpholino/mutant studies in zebrafish demonstrated that FGF3 and FGF8 redundantly induce otic placode formation, explaining why single-gene knockouts have moderate phenotypes and establishing the principle of FGF ligand redundancy in otic induction.

    Evidence Antisense morpholino knockdown combined with fgf8 (ace) genetic mutant, double depletion, otic marker in situ hybridization

    PMID:11437442

    Open questions at the time
    • Downstream signal transduction pathway in otic precursors not mapped
    • Whether redundancy extends to other FGF family members not excluded
  10. 2002 High

    Establishing that FGF3/FGF8 from rhombomere 4 are the instructive signals for both otic placode induction and hindbrain segmental identity (r5/r6) unified two developmental processes under one signaling mechanism.

    Evidence Morpholino knockdown, r4 cell transplantation, gain-of-function misexpression in zebrafish

    PMID:11959820 PMID:12121619 PMID:12135921

    Open questions at the time
    • How r4 cells restrict FGF3 expression to produce a sharp boundary undefined
    • Downstream transcription factor targets in r5/r6 specification beyond Krox20 not fully catalogued
  11. 2003 High

    Mouse Fgf3/Fgf10 double knockouts lacking otic vesicles entirely established that FGF3 and FGF10 (rather than FGF8) are the functionally redundant pair in mammalian otic induction, with a quantitative dosage requirement.

    Evidence Double knockout mouse genetics with allelic series and otic marker analysis

    PMID:12810586 PMID:14623822

    Open questions at the time
    • Whether FGF3 and FGF10 activate identical intracellular cascades in otic tissue untested
    • Cell-autonomous vs. paracrine contributions in mammals not resolved at single-cell level
  12. 2004 High

    Discovery that SOX7 and GATA-4 competitively activate FGF3 transcription through the same PS4A element, modulated by SOX2, provided the first activating transcriptional mechanism and showed context-dependent promoter occupancy.

    Evidence Reporter assay, EMSA, RNAi in ES cells, co-expression experiments

    PMID:15082719

    Open questions at the time
    • In vivo chromatin occupancy at the endogenous Fgf3 locus not shown
    • How SOX7/GATA-4 competition is resolved in specific tissues unknown
  13. 2004 High

    Demonstrating that Fgf3 from the ventral diencephalon is required for adenohypophysis specification (lim3, pit1 induction) independently of Shh expanded FGF3's known roles beyond ear to pituitary development.

    Evidence Zebrafish fgf3 (lia) null mutant analysis with marker gene expression and Shh epistasis

    PMID:15229178

    Open questions at the time
    • FGFR isoform mediating pituitary response unknown
    • Whether FGF3 acts alone or redundantly with other FGFs in mammalian pituitary not tested
  14. 2005 High

    Showing that endoderm-derived FGF3 from pharyngeal pouches is necessary and sufficient for epibranchial placode neurogenesis, acting downstream of initial placode induction, defined a new tissue-specific role for FGF3.

    Evidence Morpholino knockdown, mosaic tissue transplantation, ectopic expression, endoderm-deficient embryos in zebrafish

    PMID:16077091

    Open questions at the time
    • Receptor and intracellular pathway in epibranchial placode neurons not identified
    • Whether other FGFs compensate partially in epibranchial context unknown
  15. 2008 Medium

    Identification of human homozygous FGF3 loss-of-function mutations causing LAMM syndrome confirmed that FGF3 is essential for human inner ear, external ear, and dental development and that signal peptide integrity is critical for function.

    Evidence Sequencing of consanguineous families, co-segregation analysis, signal peptide prediction

    PMID:18435799

    Open questions at the time
    • No in vitro secretion assay performed for the mutant proteins
    • Genotype-phenotype correlation across different FGF3 mutations limited
  16. 2010 Medium

    Placing FGF3 upstream of MAPK/ERK→Pea3→Krox20 in chick hindbrain completed the signaling cascade linking FGF3 to rhombomere boundary specification.

    Evidence Morpholino knockdown in chick, ERK phosphorylation analysis, Pea3 gain/loss-of-function

    PMID:20553903

    Open questions at the time
    • Whether FGF3 activates other MAPK cascade effectors besides Pea3 not tested
    • Single-lab result awaits independent replication
  17. 2011 Medium

    Compound Fgf3/Fgf10 mutant allelic series in mouse revealed dosage-sensitive redundancy in cardiovascular development, extending FGF3 function to outflow tract, ventricular septum, epicardium, and pharyngeal arch artery morphogenesis.

    Evidence Compound mouse mutant allelic series with morphological and molecular marker analysis

    PMID:21664901

    Open questions at the time
    • FGFR mediating cardiovascular response not identified
    • Whether FGF3 cardiovascular role is direct or secondary to pharyngeal endoderm signaling unknown
  18. 2016 High

    Demonstrating that FGF3 from presomitic mesoderm restrains BMP signaling in adjacent neuroepithelium — with genetic epistasis showing BMP pathway reduction rescues Fgf3 mutant neural tube and crest defects — established FGF3 as a cross-talk node between FGF and BMP pathways during axis extension.

    Evidence Fgf3 null mouse, BMP receptor/Noggin compound mutants, BMP4 treatment of PSM progenitors in vitro

    PMID:27144312

    Open questions at the time
    • Direct molecular mechanism by which FGF3 suppresses BMP transcription/signaling not defined
    • Whether this FGF–BMP cross-talk operates in other axial tissues unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the biological function of nuclear FGF3, the structural basis of FGFR2-IIIb selectivity, and whether FGF3 plays roles in adult tissue homeostasis beyond developmental contexts.
  • Function of nuclear FGF3 isoform entirely uncharacterized
  • No crystal structure of FGF3–receptor complex
  • Adult physiological roles remain unexplored

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 6 GO:0008289 lipid binding 2
Localization
GO:0005576 extracellular region 3 GO:0031012 extracellular matrix 2 GO:0005634 nucleus 1
Pathway
R-HSA-1266738 Developmental Biology 8 R-HSA-162582 Signal Transduction 4
Partners
CTBP2FGF10FGF8FGFR2GATA4SOX6SOX7

Evidence

Reading pass · 32 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1988 FGF3 (int-2) encodes a protein with amino acid homology to the fibroblast growth factor family; four mRNA classes are generated from two alternate transcriptional start sites and two alternate polyadenylation sites, all encoding the same protein product. cDNA library construction, Northern blot hybridization, primer extension analysis, RNase protection The EMBO journal High 2841106 3416832
1986 Mouse FGF3 (int-2) gene comprises at least three exons encoding a 245 amino acid, ~27 kDa protein with homology to the fibroblast growth factor family. DNA sequencing, cDNA alignment, intron-exon boundary mapping The EMBO journal High 3013624
1989 INT-2 and kFGF (hst) proteins induce mesoderm formation in isolated Xenopus animal pole explants and stimulate DNA synthesis in mammalian fibroblasts, demonstrating growth factor / mesoderm-inducing activity. Xenopus animal cap assay, DNA synthesis assay in mammalian fibroblasts Development (Cambridge, England) High 2483371
1990 FGF3 (int-2) acts as a potent epithelial growth factor in vivo: MMTV-driven expression in transgenic mice causes mammary gland hyperplasia in females and benign epithelial hyperplasia resembling BPH in the prostate of males. Transgenic mouse overexpression, histological analysis The EMBO journal High 1690126
1993 Mice homozygous for targeted disruption of Fgf3 (int-2) develop defects in the tail (primitive streak/tail bud role) and inner ear (otic vesicle morphogenesis), establishing FGF3 as required for these developmental processes. Gene targeting / homologous recombination, loss-of-function mouse model, histological phenotyping Development (Cambridge, England) High 8223243
1994 A single CUG-initiated form of FGF3 has dual subcellular fates determined by competing signals: secretion is mediated by signal peptide cleavage, while nuclear localization is determined by a bipartite nuclear localization signal that also requires the N-terminal sequences upstream of the signal peptide. In vitro translation (reticulocyte lysate), transfection in COS-1 cells, deletion/replacement mutagenesis, heterologous fusion protein analysis The EMBO journal High 8076608
1993 Xenopus FGF3 (XFGF3) is secreted as glycosylated 31 kDa (p31) and proteolytically processed 27 kDa (p27) forms that bind heparin-Sepharose and the extracellular matrix; conditioned medium containing these proteins induces morphological transformation of NIH3T3 cells and stimulates DNA synthesis in cells expressing FGFR1/2 isoforms. COS-1 cell transfection, glycosylation analysis, heparin-Sepharose binding, cell-based mitogenicity assay, transformation assay The EMBO journal High 8223431
1996 Zebrafish FGF3 is secreted and associates with the extracellular matrix; its receptor binding preferentially for FGFR2-IIIb rather than IIIc, and C-terminal sequences determine differences in receptor affinity, mitogenic potency, and transforming activity compared to Xenopus FGF3. COS-1 transfection, heparin-release assay, receptor binding competition, mitogenicity assay, NIH3T3 transformation assay, Xenopus/zebrafish chimeric proteins Oncogene High 8622866
2001 Zebrafish fgf3 and fgf8 redundantly induce otic placode formation: depletion of either alone causes moderate reduction in otic vesicle size, while combined depletion causes near-complete loss of otic tissue and absence of early otic marker (pax8, pax2.1) expression. Antisense morpholino knockdown, genetic mutant (ace/fgf8), in situ hybridization for otic markers Developmental biology High 11437442
2002 In zebrafish, FGF3 and FGF8 act as redundant signals from rhombomere 4 to induce otic placode formation and to establish hindbrain segmental identity (rhombomeres 5 and 6); r4 transplantation and misexpression of either factor can induce r5/r6 markers. Antisense morpholino knockdown, cell transplantation, gain-of-function misexpression, in situ hybridization Development (Cambridge, England) / Current biology : CB High 11959820 12121619 12135921
2003 In mouse, Fgf3 and Fgf10 together are required for otic vesicle formation: double mutant embryos fail to form otic vesicles, with intermediate phenotypes in embryos carrying three mutant alleles, demonstrating a quantitative requirement for FGF signaling in otic induction. Double knockout mouse genetics, analysis of otic marker gene expression, cell proliferation assays Development (Cambridge, England) High 12810586 14623822
2000 Ectopic expression of FGF3 in chick embryos induces ectopic otic placodes expressing otic marker genes and forming vesicles with characteristic inner ear gene expression patterns; FGF2 had no such effect, demonstrating specificity of FGF3 in inner ear fate induction. In ovo gene transfer (chick), ectopic expression, in situ hybridization for otic markers Development (Cambridge, England) High 10769226
2007 In mouse, Fgf3 expressed in the hindbrain and prospective neurosensory domain is required for dorsal otic patterning and endolymphatic duct formation; Fgf3 acts downstream of Hoxa1/Mafb and upstream of Gbx2 in the WNT-initiated genetic cascade, and prevents ventral expansion of r5-6 Wnt3a expression. Fgf3 null mouse analysis, in situ hybridization for molecular markers, genetic epistasis placement Development (Cambridge, England) High 17855431
2004 Fgf3 signaling from the ventral diencephalon is required non-cell-autonomously to induce lim3, pit1 and other pituitary-specific genes in adenohypophyseal progenitor cells; Fgf3 does not act via Shh signaling in this context. Zebrafish lia/fgf3 null mutant analysis, in situ hybridization, genetic epistasis with Shh Development (Cambridge, England) High 15229178
2005 Endoderm-derived Fgf3, specifically from pharyngeal endodermal pouches, is necessary and sufficient for neurogenesis (phox2a-positive neurons) in zebrafish epibranchial placodes; foxi1 expression in placode precursors is independent of endoderm/Fgf3, indicating Fgf3 acts after initial placode induction. Morpholino knockdown, tissue transplantation (mosaic analysis), ectopic fgf3 expression, endoderm-deficient embryos Development (Cambridge, England) High 16077091
2001 SOX6 binds the Fgf-3 promoter element PS4A and represses Fgf-3 transcription by recruiting the co-repressor CtBP2 via a PLNLSS motif; SOX6 and Fgf-3 show mutually exclusive expression in the otic vesicle. Yeast one-hybrid screen, yeast two-hybrid, reporter gene assay, co-expression in NIH3T3, mutational analysis, in situ hybridization Nucleic acids research High 11504872
2004 SOX7 and GATA-4 are competitive activators of Fgf-3 transcription through the PS4A promoter element; SOX7 competes with GATA-4 for PS4A occupancy. SOX2 negatively modulates GATA-4-mediated activation. RNA interference against Sox7 abolishes Fgf-3 expression in GATA-4-deficient ES cells. Reporter gene assay, co-expression experiments, electrophoretic mobility shift (nuclear extracts), RNAi, ES cell differentiation, in situ hybridization The Journal of biological chemistry High 15082719
2016 PSM-derived FGF3 acts upstream of BMP signaling in the adjacent neuroepithelium during axis extension: loss of Fgf3 elevates BMP signals causing increased neuroepithelial proliferation, delayed neural tube closure, and premature neural crest specification; reducing BMP signaling (loss of BMP receptor activity) alleviates Fgf3 mutant defects, while increasing BMP (Noggin haploinsufficiency) exacerbates them. Fgf3 null mouse, genetic epistasis (BMP pathway components), BMP4 treatment of PSM progenitors in vitro, Noggin heterozygous/Fgf3 compound mutants, apoptosis manipulation PLoS genetics High 27144312
2008 In Ciona intestinalis, FGF3 from the floor plate of the nerve cord directs notochord convergent extension through non-MAPK FGF receptor signaling; dominant-negative FGFR suppresses polarized actin-rich protrusions in notochord cells and disrupts intercalation; inhibiting FGF signaling in Xenopus mesoderm explants perturbs convergent extension and disrupts membrane localization of Dishevelled. Dominant-negative FGFR expression, morpholino knockdown, live imaging of actin protrusions, Xenopus explant assay, Dishevelled localization Development (Cambridge, England) Medium 19036800
2010 In chick hindbrain, FGF3 activates the MAPK/ERK pathway and is required for upregulation of the transcription factor Pea3, which in turn is necessary for Krox20 expression in rhombomeres 3 and 5, placing FGF3 upstream of Pea3 in the Krox20 regulatory cascade. Morpholino knockdown (chick), in situ hybridization, ERK phosphorylation analysis, Pea3 gain/loss-of-function Developmental biology Medium 20553903
2008 In chick hindbrain, BMP activity suppresses FGF3 expression, and this suppression requires follistatin-mediated BMP inhibition; FGF3 expression also maintains itself via an autoregulatory loop requiring FGF receptor activity. Morpholino knockdown (follistatin), BMP overexpression, follistatin protein addition, FGFR inhibitor (SU5402), in situ hybridization Developmental biology Medium 18823972
2009 Hindbrain boundary cells are required for downregulation of segmental FGF3 expression: ablation of boundary cells (truncated EphA4 overexpression) or surgical removal of the r3/r4 boundary maintains segmental FGF3 expression at stages when it is normally restricted to boundaries, indicating a boundary-derived soluble repressive signal. Dominant-negative EphA4 overexpression, surgical boundary ablation, in situ hybridization BMC developmental biology Medium 19232109
1992 Wnt-1 and int-2 (FGF3) transgenes cooperate in mammary carcinogenesis: bitransgenic mice develop tumors earlier and with higher frequency than either single transgenic line, and Wnt-1-induced epithelial hyperplasia increases int-2 transgene expression, suggesting that Wnt-1 and FGF3 act in complementary pathways. Doubly transgenic mice, tumor incidence analysis, RNA expression analysis, in situ hybridization Molecular and cellular biology Medium 1530875
1992 In Xenopus, FGF-3 (int-2) expression is induced by mesoderm induction (bFGF/activin treatment of blastula ectoderm) and by neural induction (heterotypic grafting), and the protein can induce mesoderm from animal caps similarly to other FGFs and posteriorizes embryos. In situ hybridization, blastula ectoderm treatment, heterotypic grafting, animal cap assay Development (Cambridge, England) Medium 1425349
1994 MCF-10A cells infected with the int-2 oncogene acquire angiogenic activity, inducing blood vessel growth in the chick chorioallantoic membrane and rat mesentery; conditioned medium from int-2-infected cells is sufficient for this activity. Retroviral infection, chick CAM assay, rat mesentery angiogenesis assay, conditioned medium transfer Cancer research Medium 7505201
1998 FGF-3 production in mammary myoepithelial cells stimulates secretion of pro-MMP-9, pro-MMP-2, and plasminogen activators, promoting invasion in Matrigel; this is mechanistically distinct from FGF-4, which has no effect on these proteases. Retroviral infection of EF43 cells, invasion assay (Matrigel), zymography/proteolytic assay, in vivo tumor transplantation Oncogene Medium 9798677
2011 Fgf3 and Fgf10 have redundant and dosage-sensitive requirements in murine cardiovascular development: compound mutants show a severity series affecting outflow tract, ventricular septum, AV cushions, ventricular myocardium, epicardium, and fourth pharyngeal arch artery; molecular marker analysis shows abnormalities in each cardiovascular progenitor population without loss of specification. Compound mouse mutants (allelic series), morphological analysis, molecular marker assessment at multiple time points Developmental biology Medium 21664901
1998 Craniofacial dysmorphology (craniosynostosis, Crouzon-like) in mice results from insertional mutation between Fgf3 and Fgf4, which upregulates expression of both Fgf3 and Fgf4 in cranial sutures, confirming FGF signaling pathway involvement in craniofacial development. Retroviral insertional mutagenesis, transcript analysis, in situ hybridization, histological phenotyping Developmental dynamics Medium 9626498
2002 Inducible FGF-3 expression in the mammary gland causes ductal hyperplasia by disrupting the balance between mitogenic and apoptotic signals; RU486 withdrawal reverses the phenotype, and synergism between FGF-3 mitogenic signaling and estrogen is required for pregnancy-dependent tumorigenesis. Mifepristone-inducible binary transgenic system, histological analysis, apoptosis/proliferation markers Proceedings of the National Academy of Sciences of the United States of America Medium 12169667
2001 Inducible FGF-3 expression in adult mouse lung causes alveolar macrophage infiltration at low levels and diffuse alveolar type II cell hyperplasia at high levels; both phenotypes are reversible upon ligand withdrawal. Progesterone antagonist-responsive binary transgenic system, RU486 induction, histological analysis Proceedings of the National Academy of Sciences of the United States of America Medium 11331772
2008 Homozygous FGF3 mutations in humans (p.Leu6Pro within the signal peptide, predicted to impair secretion; and frameshift p.Ile85MetfsX15) cause LAMM syndrome (complete labyrinthine aplasia, microtia, microdontia), confirming FGF3 is required for human inner ear development and that signal peptide integrity is functionally important. Human genetics (sequencing in consanguineous families), co-segregation analysis, signal peptide prediction Clinical genetics Medium 18435799
1992 Int-2 (FGF3) acts as an autocrine or ultra-short-range paracrine growth factor in mammary epithelium: transplanted mammary tissue expressing int-2 mRNA shows abnormal growth only within the transplant, with no effect on adjacent wild-type host epithelium. Transgenic tissue transplantation, in situ hybridization for cell-specific mRNA localization, mammary whole-mount analysis Journal of the National Cancer Institute Medium 1317463

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1993 Mice homozygous for a targeted disruption of the proto-oncogene int-2 have developmental defects in the tail and inner ear. Development (Cambridge, England) 402 8223243
1988 Expression of the FGF-related proto-oncogene int-2 during gastrulation and neurulation in the mouse. The EMBO journal 392 3293998
1984 Tumorigenesis by mouse mammary tumor virus: proviral activation of a cellular gene in the common integration region int-2. Cell 349 6327073
1986 Characterization and chromosome assignment of the human homolog of int-2, a potential proto-oncogene. Molecular and cellular biology 255 3023852
1990 The int-2 gene product acts as an epithelial growth factor in transgenic mice. The EMBO journal 251 1690126
2003 Fgf3 and Fgf10 are required for mouse otic placode induction. Development (Cambridge, England) 238 12810586
1986 Sequence, topography and protein coding potential of mouse int-2: a putative oncogene activated by mouse mammary tumour virus. The EMBO journal 238 3013624
1986 Two proto-oncogenes implicated in mammary carcinogenesis, int-1 and int-2, are independently regulated during mouse development. Proceedings of the National Academy of Sciences of the United States of America 221 2429320
2001 Zebrafish fgf3 and fgf8 encode redundant functions required for otic placode induction. Developmental biology 211 11437442
2000 Associations of FGF-3 and FGF-10 with signaling networks regulating tooth morphogenesis. Developmental dynamics : an official publication of the American Association of Anatomists 210 11066089
2002 Fgf3 and Fgf8 are required together for formation of the otic placode and vesicle. Development (Cambridge, England) 202 11959820
2002 Fgf8 and Fgf3 are required for zebrafish ear placode induction, maintenance and inner ear patterning. Mechanisms of development 187 12385757
2002 FGF3 and FGF8 mediate a rhombomere 4 signaling activity in the zebrafish hindbrain. Development (Cambridge, England) 186 12135921
1989 High incidence of coamplification of hst-1 and int-2 genes in human esophageal carcinomas. Cancer research 178 2529025
1989 The mouse homolog of the hst/k-FGF gene is adjacent to int-2 and is activated by proviral insertion in some virally induced mammary tumors. Proceedings of the National Academy of Sciences of the United States of America 173 2548184
2003 Requirements for FGF3 and FGF10 during inner ear formation. Development (Cambridge, England) 172 14623822
1988 Amplification of human int-2 in breast cancers and squamous carcinomas. Oncogene 166 2895446
1995 Multiple roles for FGF-3 during cranial neural development in the chicken. Development (Cambridge, England) 161 7789270
1990 Amplification of the int-2 gene in human head and neck squamous cell carcinomas. Oncogene 160 2193294
1988 Human HST1 (HSTF1) gene maps to chromosome band 11q13 and coamplifies with the INT2 gene in human cancer. Proceedings of the National Academy of Sciences of the United States of America 158 3290903
2007 Duplication of FGF3, FGF4, FGF19 and ORAOV1 causes hair ridge and predisposition to dermoid sinus in Ridgeback dogs. Nature genetics 156 17906623
1989 Mesoderm-inducing properties of INT-2 and kFGF: two oncogene-encoded growth factors related to FGF. Development (Cambridge, England) 156 2483371
1989 The amplification unit on chromosome 11q13 in aggressive primary human breast tumors entails the bcl-1, int-2 and hst loci. Oncogene 152 2915903
1988 Multiple RNAs expressed from the int-2 gene in mouse embryonal carcinoma cell lines encode a protein with homology to fibroblast growth factors. The EMBO journal 140 2841106
2002 Establishment of hindbrain segmental identity requires signaling by FGF3 and FGF8. Current biology : CB 129 12121619
1992 Developmental expression of the Xenopus int-2 (FGF-3) gene: activation by mesodermal and neural induction. Development (Cambridge, England) 128 1425349
2013 FGF3/FGF4 amplification and multiple lung metastases in responders to sorafenib in hepatocellular carcinoma. Hepatology (Baltimore, Md.) 126 22890726
1992 Transgenes expressing the Wnt-1 and int-2 proto-oncogenes cooperate during mammary carcinogenesis in doubly transgenic mice. Molecular and cellular biology 126 1530875
2003 Fgf3 and Fgf8 dependent and independent transcription factors are required for otic placode specification. Development (Cambridge, England) 122 12668634
1992 Prevalence of amplification of the oncogenes c-myc, HER2/neu, and int-2 in one thousand human breast tumours: correlation with steroid receptors. European journal of cancer (Oxford, England : 1990) 119 1350457
1996 The role of FGF-3 in early inner ear development: an analysis in normal and kreisler mutant mice. Developmental biology 114 8631508
1994 Competition between nuclear localization and secretory signals determines the subcellular fate of a single CUG-initiated form of FGF3. The EMBO journal 110 8076608
2000 Induction of inner ear fate by FGF3. Development (Cambridge, England) 109 10769226
2004 Fgf3 signaling from the ventral diencephalon is required for early specification and subsequent survival of the zebrafish adenohypophysis. Development (Cambridge, England) 106 15229178
2003 Unique and combinatorial functions of Fgf3 and Fgf8 during zebrafish forebrain development. Development (Cambridge, England) 106 12900450
1990 Introduction of a lacZ reporter gene into the mouse int-2 locus by homologous recombination. Proceedings of the National Academy of Sciences of the United States of America 94 2120706
1990 Cathepsin D assay in primary breast cancer and lymph nodes: relationship with c-myc, c-erb-B-2 and int-2 oncogene amplification and node invasiveness. European journal of cancer (Oxford, England : 1990) 88 2141510
1991 Deletion of 17p and amplification of the int-2 gene in esophageal carcinomas. Cancer research 86 1826231
1997 EMS1 amplification can occur independently of CCND1 or INT-2 amplification at 11q13 and may identify different phenotypes in primary breast cancer. Oncogene 84 9380415
1989 Linkage analysis of multiple endocrine neoplasia type 1 with INT2 and other markers on chromosome 11. Genomics 84 2565877
2007 Differential requirements for FGF3, FGF8 and FGF10 during inner ear development. Developmental biology 82 17601531
1989 Sequence organization of the human int-2 gene and its expression in teratocarcinoma cells. Oncogene 81 2470007
1988 Coamplification of the hst-1 and int-2 genes in human cancers. Japanese journal of cancer research : Gann 79 3133332
2007 Fgf3 is required for dorsal patterning and morphogenesis of the inner ear epithelium. Development (Cambridge, England) 77 17855431
1988 Four classes of mRNA are expressed from the mouse int-2 gene, a member of the FGF gene family. The EMBO journal 77 3416832
1998 Expression and functions of FGF-3 in Xenopus development. The International journal of developmental biology 76 9879707
1996 Expression of Fgf-3 in relation to hindbrain segmentation, otic pit position and pharyngeal arch morphology in normal and retinoic acid-exposed mouse embryos. Anatomy and embryology 74 8800419
1987 The progesterone receptor gene maps to human chromosome band 11q13, the site of the mammary oncogene int-2. Proceedings of the National Academy of Sciences of the United States of America 71 3472240
1995 Visualization of INT2 and HST1 amplification in oral squamous cell carcinomas. Genes, chromosomes & cancer 69 7539284
1989 Amplification of the proto-oncogenes int-2, c-erb B-2 and c-myc in human breast cancer. Clinica chimica acta; international journal of clinical chemistry 68 2611995
1996 Gene defect in hypodontia: exclusion of EGF, EGFR, and FGF-3 as candidate genes. Journal of dental research 65 8831628
2001 SOX6 binds CtBP2 to repress transcription from the Fgf-3 promoter. Nucleic acids research 63 11504872
1988 Differential expression of two homologous and clustered oncogenes, Hst1 and Int-2, during differentiation of F9 cells. Biochemical and biophysical research communications 61 3060118
1984 Mouse mammary tumor virus integration regions int-1 and int-2 map on different mouse chromosomes. Molecular and cellular biology 61 6321961
2005 Endoderm-derived Fgf3 is necessary and sufficient for inducing neurogenesis in the epibranchial placodes in zebrafish. Development (Cambridge, England) 58 16077091
2000 Frequent c-myc and Int-2 overrepresentations in nasopharyngeal carcinoma. Human pathology 58 10685630
1990 Analysis of the int-1, int-2, c-myc, and neu oncogenes in human breast carcinomas. Cancer research 55 1975511
2002 An expanded domain of fgf3 expression in the hindbrain of zebrafish valentino mutants results in mis-patterning of the otic vesicle. Development (Cambridge, England) 53 12399318
1989 The mouse homologue of hst/k-FGF: sequence, genome organization and location relative to int-2. Nucleic acids research 53 2740210
1993 int-2 amplification in breast cancer: association with decreased survival and relationship to amplification of c-erbB-2 and c-myc. International journal of cancer 52 8449602
1987 Activation of int-1 and int-2 mammary oncogenes in hormone-dependent and -independent mammary tumors of GR mice. Journal of virology 52 3029401
2008 FGF3 in the floor plate directs notochord convergent extension in the Ciona tadpole. Development (Cambridge, England) 51 19036800
2004 SOX7 and GATA-4 are competitive activators of Fgf-3 transcription. The Journal of biological chemistry 50 15082719
1998 Crouzon-like craniofacial dysmorphology in the mouse is caused by an insertional mutation at the Fgf3/Fgf4 locus. Developmental dynamics : an official publication of the American Association of Anatomists 49 9626498
1994 Targeted disruption of int-2 (fgf-3) causes developmental defects in the tail and inner ear. Molecular reproduction and development 47 7999362
2009 Modulation of Fgf3 dosage in mouse and men mirrors evolution of mammalian dentition. Proceedings of the National Academy of Sciences of the United States of America 46 20018768
2007 SNP genome scanning localizes oto-dental syndrome to chromosome 11q13 and microdeletions at this locus implicate FGF3 in dental and inner-ear disease and FADD in ocular coloboma. Human molecular genetics 46 17656375
1993 Amplified region of chromosome band 11q13 in breast and squamous cell carcinomas encompasses three CpG islands telomeric of FGF3, including the expressed gene EMS1. Genes, chromosomes & cancer 44 7685625
1996 The zebrafish Fgf-3 gene: cDNA sequence, transcript structure and genomic organization. Gene 43 8654946
2011 Redundant and dosage sensitive requirements for Fgf3 and Fgf10 in cardiovascular development. Developmental biology 41 21664901
2008 Homozygous FGF3 mutations result in congenital deafness with inner ear agenesis, microtia, and microdontia. Clinical genetics 41 18435799
1988 Two homologous oncogenes, HST1 and INT2, are closely located in human genome. Biochemical and biophysical research communications 41 2974287
2016 An FGF3-BMP Signaling Axis Regulates Caudal Neural Tube Closure, Neural Crest Specification and Anterior-Posterior Axis Extension. PLoS genetics 40 27144312
1991 GST pi gene is frequently coamplified with INT2 and HSTF1 proto-oncogenes in human breast cancers. Oncogene 40 1826346
1993 Ha-ras and v-raf oncogenes, but not int-2 and c-myc, interfere with the lactogenic hormone dependent activation of the mammary gland specific transcription factor. Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research 39 8424907
1995 Gene amplification for c-erbB-2, c-myc, epidermal growth factor receptor, int-2, and N-myc measured by quantitative PCR with a multiple competitor template. Clinical chemistry 38 7768000
1995 DNA amplification of HER-2/neu and INT-2 oncogenes in epithelial ovarian cancer. Gynecologic oncology 38 8522248
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1992 Int-2, an autocrine and/or ultra-short-range effector in transgenic mammary tissue transplants. Journal of the National Cancer Institute 35 1317463
2001 Phenotypic consequences of lung-specific inducible expression of FGF-3. Proceedings of the National Academy of Sciences of the United States of America 32 11331772
1993 FGF3 from Xenopus laevis. The EMBO journal 32 8223431
1991 Her-2/neu and INT2 proto-oncogene amplification in malignant breast tumors in relation to reproductive factors and exposure to exogenous hormones. Journal of the National Cancer Institute 32 1920494
1988 The FGF-related oncogene, K-FGF, maps to human chromosome region 11q13, possibly near int-2. Oncogene research 32 3060803
1993 First experience with FGF-3 (INT-2) amplification in women with epithelial ovarian cancer. British journal of cancer 31 8494710
2008 Inhibition of BMPs by follistatin is required for FGF3 expression and segmental patterning of the hindbrain. Developmental biology 30 18823972
1996 Meanings of c-erbB and int-2 amplification in superficial esophageal squamous cell carcinomas. The Annals of thoracic surgery 30 8784015
1990 Insertion mutation of the int-1 and int-2 loci by mouse mammary tumor virus in premalignant and malignant neoplasms from the GR mouse strain. Journal of virology 30 2157060
2009 Boundary cells regulate a switch in the expression of FGF3 in hindbrain rhombomeres. BMC developmental biology 29 19232109
2008 Syndromic congenital sensorineural deafness, microtia and microdontia resulting from a novel homoallelic mutation in fibroblast growth factor 3 (FGF3). European journal of human genetics : EJHG 28 18701883
1998 FGF-3 and FGF-4 elicit distinct oncogenic properties in mouse mammary myoepithelial cells. Oncogene 28 9798677
1990 Proviral insertions within the int-2 gene can generate multiple anomalous transcripts but leave the protein-coding domain intact. Journal of virology 28 2153243
1989 The structure and function of the int-2 oncogene. Progress in growth factor research 27 2491259
2017 Hypomethylated Fgf3 is a potential biomarker for early detection of oral cancer in mice treated with the tobacco carcinogen dibenzo[def,p]chrysene. PloS one 26 29073177
2010 Analysis of expression and function of FGF-MAPK signaling components in the hindbrain reveals a central role for FGF3 in the regulation of Krox20, mediated by Pea3. Developmental biology 25 20553903
2000 FGF4 and INT2 oncogenes are amplified and expressed in Kaposi's sarcoma. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 25 10786811
1994 MCF-10A cells infected with the int-2 oncogene induce angiogenesis in the chick chorioallantoic membrane and in the rat mesentery. Cancer research 25 7505201
1996 Secretion and mitogenic activity of zebrafish FGF3 reveal intermediate properties relative to mouse and Xenopus homologues. Oncogene 24 8622866
1993 Growth-stimulating activity of interleukin 6 on human mammary epithelial cells transfected with the int-2 gene. Cancer research 24 8100482
1991 Host genetic background effect on the frequency of mouse mammary tumor virus-induced rearrangements of the int-1 and int-2 loci in mouse mammary tumors. Journal of virology 24 1712864
2002 Inducible expression of FGF-3 in mouse mammary gland. Proceedings of the National Academy of Sciences of the United States of America 22 12169667