Affinage

GNA12

Guanine nucleotide-binding protein subunit alpha-12 · UniProt Q03113

Length
381 aa
Mass
44.3 kDa
Annotated
2026-06-10
100 papers in source corpus 13 papers cited in narrative 13 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GNA12 encodes Gα12, the α-subunit of the G12 heterotrimeric G protein (the gep proto-oncogene), which couples GPCR activation — notably LPA receptors — to a transcriptional program driving cell proliferation and neoplastic transformation (PMID:21901169, PMID:26413218). Upon activation, Gα12 engages multiple effector routes: it associates with the scaffold protein JLP through JLP's C-terminal domain to drive JNK activation, an interaction required for Gα12/Gα13-mediated transformation (PMID:21472140); it phosphorylates and activates STAT3 at Tyr705 (via JAK3/Src) and Ser727 (via PDGFRα/PI3K), with STAT3 acting as a critical mediator of transformation (PMID:16247467); and it stimulates CREB phosphorylation at Ser133 through a cAMP-independent, Ras-ERK-dependent route that supports LPA-driven proliferation (PMID:24055910). Through Rho/Rac-dependent activation of AP-1 (c-Jun), Gα12 upregulates TGFβ1 transcription (PMID:19151758), and it activates the Hippo-pathway coactivator YAP to promote ovarian cancer cell growth (PMID:26804165). In hepatocellular carcinoma, activated Gα12 drives epithelial-mesenchymal transition by inducing MDM2 through AP-1/c-Jun, lowering p53 and thereby derepressing ZEB1 via the p53-responsive miR-200/192/215 microRNA clusters (PMID:25065598). GNA12 expression is itself positively controlled by c-Jun binding to a minimal 784 bp promoter region (PMID:28394299). In vivo, silencing Gα12 (and Gα13) reduces xenograft tumor growth, establishing the G12 family α-subunits as determinants of tumor growth (PMID:26413218).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2006 Medium

    Established that activated Gα12 transforms cells through STAT3, identifying a defined downstream effector for gep oncogene-driven transformation.

    Evidence Constitutively active Gα12QL transfection with phospho-STAT3 immunoblotting, dominant-negative STAT3 co-expression, foci and soft-agar assays

    PMID:16247467

    Open questions at the time
    • Single lab; mechanism of how Gα12 engages JAK3/Src and PDGFRα not resolved
    • STAT3 transcriptional targets in this context not defined
  2. 2008 Low

    Tested whether GNA12 physically interacts with regulators and contributes to germ cell biology, linking it to RGS22 in the testis.

    Evidence Co-immunoprecipitation of GNA12 with RGS22, GFP-fusion tracking, immunofluorescence and testis histology

    PMID:18703424

    Open questions at the time
    • Single Co-IP for the GNA12 interaction without reciprocal validation
    • Localization and phenotype data were for GNA13, not GNA12
    • No functional manipulation of GNA12
  3. 2008 Low

    Excluded GNA12 as the causal gene for familial hyperaldosteronism type II in 7p22-linked families, a negative genetic result.

    Evidence DNA sequencing of GNA12 coding regions in FH-II family members

    PMID:18307725

    Open questions at the time
    • Small cohort; coding-region only
    • Does not address regulatory or non-coding variants
  4. 2009 High

    Defined how Gα12/13 reprograms transcription, showing Rho/Rac-AP-1-dependent upregulation of TGFβ1.

    Evidence siRNA knockdown, knockout MEFs, activated mutant rescue, promoter-deletion reporter, AP-1 assay, dominant-negative Rho/Rac/Cdc42

    PMID:19151758

    Open questions at the time
    • Effector linking Gα12 to Rho/Rac not specified
    • Physiological consequence of TGFβ1 induction not tracked in vivo
  5. 2011 Medium

    Identified JLP as a Gα12-binding scaffold required for JNK activation and transformation, providing a physical effector link.

    Evidence Co-IP, competitive inhibition with JLP C-terminal domain peptide, JNK activity assay, foci formation assay

    PMID:21472140

    Open questions at the time
    • Single lab; structural basis of the interaction not resolved
    • How JLP couples to the JNK module downstream not detailed
  6. 2011 Medium

    Demonstrated that LPA drives ovarian cancer proliferation specifically through Gα12, separating proliferative from migratory signaling.

    Evidence shRNA silencing, inhibitory CT12 minigene disrupting LPAR-Gα12, proliferation and migration assays across multiple cell lines

    PMID:21901169

    Open questions at the time
    • Downstream proliferative effectors not defined here
    • Single lab
  7. 2013 Medium

    Showed Gα12 mediates LPA-stimulated CREB activation via a cAMP-independent Ras-ERK route supporting proliferation.

    Evidence Constitutively active Gα12, siRNA silencing, phospho-CREB (Ser133) immunoblotting, dominant-negative CREB(S133A), proliferation assay

    PMID:24055910

    Open questions at the time
    • Link between Gα12 and Ras not mechanistically resolved
    • CREB target genes not identified
  8. 2014 High

    Connected Gα12 to EMT in HCC through an AP-1/MDM2/p53/miRNA axis derepressing ZEB1, defining a transcriptional EMT mechanism.

    Evidence Gα12QL transfection, miRNome and cDNA profiling, miRNA mimics, shRNA knockdown, xenograft tumor model

    PMID:25065598

    Open questions at the time
    • Whether the same axis operates in non-HCC tumors not established
    • Proximal effector linking Gα12 to AP-1/MDM2 not fully mapped
  9. 2015 Medium

    Established Gα12/13 as the determinant α-subunits for ovarian tumor growth in vivo, distinguishing them from Gαi2/Gαq.

    Evidence siRNA silencing of individual Gα subunits, proliferation and invasion assays, xenograft model with survival analysis

    PMID:26413218

    Open questions at the time
    • Gα13 effect was stronger than Gα12; relative contributions not dissected mechanistically
    • Single lab
  10. 2015 Low

    Linked GNA12 promoter hypomethylation to elevated expression in preeclampsia, implicating epigenetic control of GNA12.

    Evidence MassARRAY CpG methylation analysis of placenta and blood DNA with RT-qPCR

    PMID:26767593

    Open questions at the time
    • Correlative association without functional manipulation
    • Causal direction between methylation and expression not tested
  11. 2016 High

    Showed Gα12/13 selectively activates the Hippo coactivator YAP to drive ovarian cancer growth, adding a transcriptional growth effector.

    Evidence Chimeric G protein/DREADD selective pathway activation, YAP assays, shRNA knockdown, YAP inhibitor, growth assay

    PMID:26804165

    Open questions at the time
    • Upstream Hippo kinase steps engaged by Gα12 not delineated
    • Single study
  12. 2017 Medium

    Identified c-Jun as a specific transcriptional regulator of GNA12, revealing a feedforward loop with AP-1-dependent Gα12 signaling.

    Evidence Promoter cloning, luciferase deletion analysis, ChIP, c-Jun siRNA, RT-qPCR and immunoblotting in PC3 cells

    PMID:28394299

    Open questions at the time
    • Roles of the co-identified C/EBP and CREB1 sites not functionally tested
    • Single cell-type/single lab
  13. 2021 Low

    Tested post-transcriptional regulation of GNA12, showing a plant-derived miRNA can lower GNA12 and modulate downstream mTOR signaling.

    Evidence Bioinformatic prediction and synthetic miR171vr transfection in HEK293 with RT-qPCR/immunoblot

    PMID:33386590

    Open questions at the time
    • No 3'UTR reporter or rescue to confirm direct targeting
    • Physiological relevance of plant miRNA targeting unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the diverse Gα12 effector branches (JLP-JNK, STAT3, CREB, Rho/Rac-AP-1, YAP, p53-miRNA) are integrated and selected in a given cell context remains unresolved.
  • No unified model of effector selection downstream of Gα12
  • Structural/biochemical basis for differential effector engagement undefined
  • Limited in vivo validation outside xenograft models

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 3 GO:0098772 molecular function regulator activity 3 GO:0003924 GTPase activity 2
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-1643685 Disease 2
Partners
JLPRGS22

Evidence

Reading pass · 13 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2006 The GTPase-deficient activated mutant of Gα12 (gep oncogene) activates STAT3 via phosphorylation at Tyrosine-705 (through JAK3 and Src kinase) and Serine-727 (through PDGFRα and PI3K). Dominant-negative STAT3 inhibits foci formation and anchorage-independent growth of Gα12QL-transfectants, establishing STAT3 as a critical mediator of Gα12-driven neoplastic transformation. Constitutively active Gα12QL transfection, phospho-STAT3 immunoblotting, dominant-negative STAT3 co-expression, foci formation and soft-agar colony assays Oncogene Medium 16247467
2009 Gα12 and Gα13 (gep oncogenes) upregulate TGFβ1 gene expression through a Rho/Rac-dependent increase in AP-1 (c-Jun) transcriptional activity. Knockdown or knockout of Gα12/Gα13 in murine embryonic fibroblasts and hepatic stellate cells reduced constitutive and thrombin-inducible TGFβ1 expression; activated mutants rescued expression in knockout cells. Dominant-negative Rho or Rac (but not Cdc42) prevented gene transactivation. siRNA knockdown, knockout MEFs, activated mutant transfection, promoter-deletion reporter assay, AP-1 activity assay, dominant-negative Rho/Rac/Cdc42 co-expression Oncogene High 19151758
2011 The scaffold protein JLP (JNK-interacting leucine zipper protein) physically associates with Gα12, and this interaction is enhanced by receptor- or mutation-mediated Gα12 activation. JLP binds Gα12 through its C-terminal domain. Disruption of the Gα12-JLP interaction (using C-terminal domain as competitive inhibitor) abrogates Gα12-stimulated JNK activation and prevents Gα12- and Gα13-mediated neoplastic transformation. Co-immunoprecipitation, competitive inhibition with C-terminal domain peptide, JNK activity assay, neoplastic transformation (foci formation) assay Neoplasia Medium 21472140
2011 LPA stimulates proliferation of ovarian cancer cells via Gα12 (the gep proto-oncogene). LPA activates Gα12 rapidly in SKOV-3 cells. An inhibitory minigene (CT12) disrupting LPAR-Gα12 interaction and shRNA silencing of Gα12 drastically attenuate LPA-mediated proliferation of SKOV3, Hey, and OVCAR-3 cells. Silencing Gα12 does not significantly affect LPA-mediated migration, indicating a proliferation-specific role. shRNA silencing, inhibitory minigene (CT12) expression, cell proliferation assay, migration assay, Gα12 activation assay Genes & cancer Medium 21901169
2013 Gα12 (gep proto-oncogene) mediates LPA-stimulated activation of CREB in ovarian cancer cells through a cAMP-independent, Ras-ERK-dependent mechanism. LPA-stimulated CREB phosphorylation at Ser133 is detected within 3 minutes. Constitutively active Gα12 stimulates CREB even without LPA; silencing Gα12 attenuates LPA-stimulated CREB phosphorylation. Expression of dominant-negative CREB (S133A) reduces LPA-stimulated proliferation of HeyA8 cells. Protein/DNA array analysis, constitutively active Gα12 expression, Gα12 siRNA silencing, phospho-CREB immunoblotting, dominant-negative CREB (S133A) expression, proliferation assay Cellular signalling Medium 24055910
2014 Gα12 overexpression in HCC causes ZEB1 induction by deregulating p53-responsive microRNA clusters (miR-200b/a/429, miR-194-2/192, miR-194-1/215) via AP-1/c-Jun-mediated MDM2 induction that reduces p53 levels. This promotes epithelial-mesenchymal transition. Sustained knockdown of Gα12 in SK-Hep1 cells (mesenchymal-type) decreased xenograft tumor growth rate and volume. Transfection with miR-200b, -192 or -215 mimic prevented Gα12QL-induced tumor cell migration/invasion. Activated Gα12QL transfection, miRNome profiling, cDNA microarray, miRNA mimic transfection, Gα12 shRNA knockdown, xenograft tumor model, integrative miRNA-mRNA network analysis Oncogene High 25065598
2015 Silencing of Gα12 and Gα13 (gep oncogenes) drastically attenuates serum- or LPA-stimulated proliferation of SKOV3 ovarian cancer cells. In xenograft models, silencing of Gα13 drastically reduced tumor growth and prolonged mouse survival; silencing of Gα12 had a similar but reduced effect. Silencing of Gαi2 or Gαq had no such effect, establishing Gα12/13 as the determinant α-subunits for ovarian cancer growth in vivo. siRNA silencing of individual Gα-subunits, proliferation assay, invasion/migration assay, xenograft tumor model with survival analysis Genes & cancer Medium 26413218
2016 Gα12/13 (encoded by GNA12/GNA13; gep oncogene) promotes proliferation of ovarian cancer cells by activating the transcriptional coactivator YAP, a component of the Hippo signaling pathway. A synthetic biology approach using chimeric G proteins and designer GPCRs confirmed selective Gα12/13 signaling to YAP. YAP inhibition by shRNA or a specific inhibitor prevented ovarian cancer cell growth. Chimeric G protein/designer GPCR (DREADD) approach for selective pathway activation, YAP activity assays, shRNA knockdown, YAP-specific inhibitor treatment, cell growth assay Oncogene High 26804165
2017 c-Jun transcription factor binds to the GNA12 5' regulatory region and controls GNA12 transcription in prostate cancer cells. Deletion analysis identified a minimal 784 bp promoter region with c-Jun, C/EBP, and CREB1 binding sites. siRNA silencing of c-Jun reduced GNA12 reporter activity, mRNA, and protein levels in PC3 cells but did not reduce GNA13 levels, indicating specific regulation of GNA12. GNA12 promoter cloning, luciferase reporter assays with deletion analysis, siRNA knockdown of c-Jun, chromatin immunoprecipitation (ChIP), RT-qPCR and immunoblotting Molecules Medium 28394299
2008 RGS22, a testis-specific regulator of G-protein signaling, physically interacts with GNA12 (and GNA13 and GNA11). GNA13 and RGS22 co-localize in the nucleus from the elongated spermatid stage onward. Defective GNA13 expression was found in macrocephalic and globozoospermic spermatozoa, suggesting a functional role for GNA12/13 and RGS22 in spermiogenesis. Co-immunoprecipitation (GNA12 interaction with RGS22), GFP-fusion protein tracking, indirect immunofluorescence, testis histology Biology of reproduction Low 18703424
2015 The GNA12 promoter is hypomethylated at specific CpG sites in placenta and peripheral blood of preeclampsia patients compared to normal pregnant women, and this hypomethylation is associated with elevated GNA12 mRNA expression in placenta, suggesting epigenetic regulation of GNA12 expression via promoter methylation. MassARRAY methylation analysis of GNA12 promoter CpG sites in placenta and blood DNA, RT-qPCR for GNA12 mRNA Annals of human genetics Low 26767593
2021 A plant microRNA isoform (miR171vr) targets the human GNA12 transcript. Treatment of HEK293 cells with synthetic miR171vr significantly decreased GNA12 mRNA and protein levels, and modulated downstream GNA12 signaling factors including mTOR. Bioinformatics prediction of miRNA-mRNA interaction, synthetic microRNA transfection into HEK293 cells, RT-qPCR and immunoblotting for GNA12 and downstream signaling components Molecular biology reports Low 33386590
2008 Examination of the GNA12 gene in familial hyperaldosteronism type II (FH-II) patients linked to chromosome 7p22 found no causative mutations in GNA12, providing a negative result for GNA12 as the causal gene for FH-II in the families studied. DNA sequencing of GNA12 coding regions in affected and unaffected members of 7p22-linked FH-II families Clinical and experimental pharmacology & physiology Low 18307725

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2003 Treatment of patients with gastro-entero-pancreatic (GEP) tumours with the novel radiolabelled somatostatin analogue [177Lu-DOTA(0),Tyr3]octreotate. European journal of nuclear medicine and molecular imaging 325 12634971
2012 Current Trends of the Incidence and Pathological Diagnosis of Gastroenteropancreatic Neuroendocrine Tumors (GEP-NETs) in Korea 2000-2009: Multicenter Study. Cancer research and treatment 190 23091441
2007 Cartilage oligomeric matrix protein associates with granulin-epithelin precursor (GEP) and potentiates GEP-stimulated chondrocyte proliferation. The Journal of biological chemistry 117 17307734
2016 The Impact of PD-L1 Expression in Patients with Metastatic GEP-NETs. Journal of Cancer 108 26958083
2000 Interferon in the management of neuroendocrine GEP-tumors: a review. Digestion 105 10940694
2001 ARF-GEP(100), a guanine nucleotide-exchange protein for ADP-ribosylation factor 6. Proceedings of the National Academy of Sciences of the United States of America 97 11226253
2009 ADAMTS-7, a direct target of PTHrP, adversely regulates endochondral bone growth by associating with and inactivating GEP growth factor. Molecular and cellular biology 95 19487464
2017 Role of PD-L1 expression as a biomarker for GEP neuroendocrine neoplasm grading. Cell death & disease 93 28837143
1999 nRap GEP: a novel neural GDP/GTP exchange protein for rap1 small G protein that interacts with synaptic scaffolding molecule (S-SCAM). Biochemical and biophysical research communications 91 10548487
2020 Comprehensive Genomic Profiling of Gastroenteropancreatic Neuroendocrine Neoplasms (GEP-NENs). Clinical cancer research : an official journal of the American Association for Cancer Research 85 32883742
1984 Immunocytochemical investigation of the gastro-entero-pancreatic (GEP) neurohormonal peptides in the pancreas and gastrointestinal tract of the dogfish Squalus acanthias. Histochemistry 85 6370932
1989 Chromogranin A (CgA) in the gastro-entero-pancreatic (GEP) endocrine system. II. CgA in mammalian entero-endocrine cells. Histochemistry 79 2807986
2016 Gastroenteropancreatic neuroendocrine tumours (GEP-NET) - Imaging and staging. Best practice & research. Clinical endocrinology & metabolism 75 26971843
2008 A GEP-ISFG collaborative study on the optimization of an X-STR decaplex: data on 15 Iberian and Latin American populations. International journal of legal medicine 73 19082839
2012 Peptide receptor radionuclide therapy (PRRT) for GEP-NETs. Best practice & research. Clinical gastroenterology 63 23582925
2019 Role of Combined [68Ga]Ga-DOTA-SST Analogues and [18F]FDG PET/CT in the Management of GEP-NENs: A Systematic Review. Journal of clinical medicine 61 31337043
2018 Investigation of receptor radionuclide therapy with 177Lu-DOTATATE in patients with GEP-NEN and a high Ki-67 proliferation index. European journal of nuclear medicine and molecular imaging 61 29387927
2005 Lysophosphatidic acid and endothelin-induced proliferation of ovarian cancer cell lines is mitigated by neutralization of granulin-epithelin precursor (GEP), a prosurvival factor for ovarian cancer. Oncogene 61 16044162
2012 Chemotherapy in gastroenteropancreatic (GEP) neuroendocrine carcinomas (NEC): a critical view. Cancer treatment reviews 57 22819619
2007 Peptide receptor expression in GEP-NET. Virchows Archiv : an international journal of pathology 54 17684767
2019 PD-L1 Expression and Immune Cell Infiltration in Gastroenteropancreatic (GEP) and Non-GEP Neuroendocrine Neoplasms With High Proliferative Activity. Frontiers in oncology 53 31134150
2018 Current treatment strategies for patients with advanced gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Clinical diabetes and endocrinology 51 30009041
2015 Feasibility and utility of re-treatment with (177)Lu-DOTATATE in GEP-NENs relapsed after treatment with (90)Y-DOTATOC. European journal of nuclear medicine and molecular imaging 48 26112388
2014 Parathyroid hormone-related peptide (PTHrP) secretion by gastroenteropancreatic neuroendocrine tumors (GEP-NETs): clinical features, diagnosis, management, and follow-up. The Journal of clinical endocrinology and metabolism 47 24905065
1986 Immunocytochemical identification and localization of peptide hormones in the gastro-entero-pancreatic (GEP) endocrine system of the mouse and a stomachless fish, Barbus conchonius. Histochemistry 46 2873113
1989 Chromogranins in mammalian GEP endocrine cells: their distribution and interrelations with co-stored amines and peptides. Archives of histology and cytology 45 2510808
2014 Gα12 gep oncogene deregulation of p53-responsive microRNAs promotes epithelial-mesenchymal transition of hepatocellular carcinoma. Oncogene 44 25065598
2021 Predictive modeling of swell-strength of expansive soils using artificial intelligence approaches: ANN, ANFIS and GEP. Journal of environmental management 42 33831756
2017 Hormone secreting gastro-entero-pancreatic neuroendocrine neoplasias (GEP-NEN): When to consider, how to diagnose? Reviews in endocrine & metabolic disorders 42 29256148
2021 Predictive Modeling of Mechanical Properties of Silica Fume-Based Green Concrete Using Artificial Intelligence Approaches: MLPNN, ANFIS, and GEP. Materials (Basel, Switzerland) 41 34947124
2002 Results of the 1999-2000 collaborative exercise and proficiency testing program on mitochondrial DNA of the GEP-ISFG: an inter-laboratory study of the observed variability in the heteroplasmy level of hair from the same donor. Forensic science international 39 11852196
2020 mTOR Pathway in Gastroenteropancreatic Neuroendocrine Tumor (GEP-NETs). Frontiers in endocrinology 38 33304317
2011 Lysophosphatidic Acid Stimulates the Proliferation of Ovarian Cancer Cells via the gep Proto-Oncogene Gα(12). Genes & cancer 36 21901169
2007 Inhibition of PC cell-derived growth factor (PCDGF)/granulin-epithelin precursor (GEP) decreased cell proliferation and invasion through downregulation of cyclin D and CDK4 and inactivation of MMP-2. BMC cancer 34 17261172
2000 The 1998-1999 collaborative exercises and proficiency testing program on DNA typing of the Spanish and Portuguese Working Group of the International Society for Forensic Genetics (GEP-ISFG). Forensic science international 34 10924847
2016 GEP oncogene promotes cell proliferation through YAP activation in ovarian cancer. Oncogene 33 26804165
2021 Plant miR171 modulates mTOR pathway in HEK293 cells by targeting GNA12. Molecular biology reports 32 33386590
2021 Validation of CP-GEP (Merlin Assay) for predicting sentinel lymph node metastasis in primary cutaneous melanoma patients: A U.S. cohort study. International journal of dermatology 32 33914348
2004 Feasibility of somatostatin receptor scintigraphy in the detection of occult primary gastro-entero-pancreatic (GEP) neuroendocrine tumours. Nuclear medicine communications 32 15100502
2015 GEP-NETs update: Biotherapy for neuroendocrine tumours. European journal of endocrinology 31 25430657
2014 PET and PET/CT with 68gallium-labeled somatostatin analogues in Non GEP-NETs Tumors. TheScientificWorldJournal 30 24693229
2013 Bone metastases in GEP-NET: response and long-term outcome after PRRT from a follow-up analysis. American journal of nuclear medicine and molecular imaging 30 24116352
2010 Yttrium-90 DOTATOC therapy in GEP-NET and other SST2 expressing tumors: a selected review. Annals of nuclear medicine 30 21107762
1997 Biochemical diagnosis of neuroendocrine GEP tumor. The Yale journal of biology and medicine 30 9825477
2019 Relationship between clinical features, GEP class, and PRAME expression in uveal melanoma. Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie 29 31065847
2003 The 2000-2001 GEP-ISFG Collaborative Exercise on mtDNA: assessing the cause of unsuccessful mtDNA PCR amplification of hair shaft samples. Forensic science international 29 12842357
2008 Examination of chromosome 7p22 candidate genes RBaK, PMS2 and GNA12 in familial hyperaldosteronism type II. Clinical and experimental pharmacology & physiology 27 18307725
2013 The gep proto-oncogene Gα13 mediates lysophosphatidic acid-mediated migration of pancreatic cancer cells. Pancreas 25 23508014
2007 IL-6-174 C/G polymorphism in the gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Experimental and molecular pathology 25 17950274
2014 SEOM clinical guidelines for the diagnosis and treatment of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) 2014. Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico 24 25183048
2008 RGS22, a novel testis-specific regulator of G-protein signaling involved in human and mouse spermiogenesis along with GNA12/13 subunits. Biology of reproduction 24 18703424
2002 Localization of mRNAs for subfamily of guanine nucleotide-exchange proteins (GEP) for ARFs (ADP-ribosylation factors) in the brain of developing and mature rats under normal and postaxotomy conditions. Brain research. Molecular brain research 24 11834294
2016 High VEGF serum values are associated with locoregional spread of gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Molecular and cellular endocrinology 23 26805636
2009 The gep oncogenes, Galpha(12) and Galpha(13), upregulate the transforming growth factor-beta1 gene. Oncogene 23 19151758
2006 Neoplastic transformation by the gep oncogene, Galpha12, involves signaling by STAT3. Oncogene 23 16247467
2019 The Correlation Between [68Ga]DOTATATE PET/CT and Cell Proliferation in Patients With GEP-NENs. Molecular imaging and biology 22 30796708
2022 Toluene Tolerated Li9.88GeP1.96Sb0.04S11.88Cl0.12 Solid Electrolyte toward Ultrathin Membranes for All-Solid-State Lithium Batteries. Nano letters 21 36535024
2017 Radioguided surgery with radiolabeled somatostatin analogs: not only in GEP-NETs. Nuclear medicine review. Central & Eastern Europe 21 28218348
2014 XBP1S, a BMP2-inducible transcription factor, accelerates endochondral bone growth by activating GEP growth factor. Journal of cellular and molecular medicine 21 24636354
2006 Analysis of body fluid mixtures by mtDNA sequencing: An inter-laboratory study of the GEP-ISFG working group. Forensic science international 21 16899347
2022 Predictive modeling of Persian walnut (Juglans regia L.) in vitro proliferation media using machine learning approaches: a comparative study of ANN, KNN and GEP models. Plant methods 18 35410228
2021 In Situ Formed Li-Ag Alloy Interface Enables Li10GeP2S12-Based All-Solid-State Lithium Batteries. ACS applied materials & interfaces 18 34648706
2005 Results of the 2003-2004 GEP-ISFG collaborative study on mitochondrial DNA: focus on the mtDNA profile of a mixed semen-saliva stain. Forensic science international 18 16243467
1980 Endocrine GEP-cells in primary testicular teratoma. Virchows Archiv. A, Pathological anatomy and histology 17 6108001
2023 Tissue-specific collagen hydroxylation at GEP/GDP triplets mediated by P4HA2. Matrix biology : journal of the International Society for Matrix Biology 16 37003347
2017 c-Jun Contributes to Transcriptional Control of GNA12 Expression in Prostate Cancer Cells. Molecules (Basel, Switzerland) 16 28394299
2017 Natural History of MEN1 GEP-NET: Single-Center Experience After a Long Follow-Up. World journal of surgery 16 28429092
2016 Genomic Profiling of Metastatic Gastroenteropancreatic Neuroendocrine Tumor (GEP-NET) Patients in the Personalized-Medicine Era. Journal of Cancer 16 27326246
2014 GEP-NETS update: functional localisation and scintigraphy in neuroendocrine tumours of the gastrointestinal tract and pancreas (GEP-NETs). European journal of endocrinology 16 24723670
2007 2006 GEP-ISFG collaborative exercise on mtDNA: reflections about interpretation, artefacts, and DNA mixtures. Forensic science international. Genetics 16 19083807
2006 GEP associates with wild-type p53 in hepatocellular carcinoma. Oncology reports 16 16685387
2015 Determinant role for the gep oncogenes, Gα12/13, in ovarian cancer cell proliferation and xenograft tumor growth. Genes & cancer 15 26413218
2013 The gep proto-oncogene Gα12 mediates LPA-stimulated activation of CREB in ovarian cancer cells. Cellular signalling 15 24055910
2024 The LUTADOSE trial: tumour dosimetry after the first administration predicts progression free survival in gastro-entero-pancreatic neuroendocrine tumours (GEP NETs) patients treated with [177Lu]Lu-DOTATATE. European journal of nuclear medicine and molecular imaging 14 39235614
2022 Peptide Receptor Radionuclide Therapy with [177Lu]Lu-DOTA-TATE in Patients with Advanced GEP NENS: Present and Future Directions. Cancers 14 35158852
2009 Forensic analysis of dog (Canis lupus familiaris) mitochondrial DNA sequences: an inter-laboratory study of the GEP-ISFG working group. Forensic science international. Genetics 13 19948334
2021 Current status and future prospects of PET-imaging applications in patients with gastro-entero-pancreatic neuroendocrine tumors (GEP-NETs). European journal of radiology 12 34482177
2015 Preeclampsia is Associated with Decreased Methylation of the GNA12 Promoter. Annals of human genetics 12 26767593
2011 Neoplastic transformation induced by the gep oncogenes involves the scaffold protein JNK-interacting leucine zipper protein. Neoplasia (New York, N.Y.) 12 21472140
2011 GEP constitutes a negative feedback loop with MyoD and acts as a novel mediator in controlling skeletal muscle differentiation. Cellular and molecular life sciences : CMLS 12 22179841
2021 [177Lu]Lu-DOTA-TATE versus standard of care in adult patients with gastro-enteropancreatic neuroendocrine tumours (GEP-NETs): a cost-consequence analysis from an Italian hospital perspective. European journal of nuclear medicine and molecular imaging 11 34950969
1990 Therapeutic strategies in the management of endocrine GEP tumours. European journal of clinical investigation 11 1702388
2022 Novel therapeutic approaches in GEP-NETs based on genetic and epigenetic alterations. Biochimica et biophysica acta. Reviews on cancer 10 36152904
2022 Effect of Solvents on a Li10GeP2S12-Based Composite Electrolyte via Solution Method for Solid-State Battery Applications. ACS applied materials & interfaces 10 36197083
2021 Immunotherapy for gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs): a 2021 update. Cancer immunology, immunotherapy : CII 10 34471940
2020 Chronic Use of Long-Acting Somatostatin Analogues (SSAs) and Exocrine Pancreatic Insufficiency (EPI) in Patients with Gastroenteropancreatic Neuroendocrine Tumors (GEP-NETs): An Under-recognized Adverse Effect. Cancer medicine journal 10 32405630
2018 Metabolic Discrimination of Different Rhodiola Species Using 1H-NMR and GEP Combinational Chemometrics. Chemical & pharmaceutical bulletin 10 30518724
2014 Systemic therapeutic strategies for GEP-NETS: what can we expect in the future? Cancer metastasis reviews 10 24375390
2003 Results of the GEP-ISFG collaborative study on the Y chromosome STRs GATA A10, GATA C4, GATA H4, DYS437, DYS438, DYS439, DYS460 and DYS461: population data. Forensic science international 10 12927417
2025 Risk stratification using the Merlin Assay (CP-GEP) in an independent cohort of 930 patients with clinical stage I/II melanoma who did not undergo sentinel lymph node biopsy. European journal of cancer (Oxford, England : 1990) 9 40274320
2022 Comparative Metastatic Rates in GEP Class 1A versus 1B Posterior Uveal Melanoma: Results Contrary to Expectations. Ocular oncology and pathology 9 36925732
2020 c-MET inhibition: novel treatment for sporadic and MEN1-associated GEP NETs. Journal of molecular endocrinology 9 32384260
1979 Majority and minority cell populations in GEP and bronchial endocrine tumours. Scandinavian journal of gastroenterology. Supplement 9 225792
2023 Prospective Multicentric Assessment of 68Ga-DOTANOC PET/CT in Grade 1-2 GEP-NET. Cancers 8 36672462
2023 Defining Tumor Microenvironment as a Possible Target for Effective GEP-NENs Immunotherapy-A Systematic Review. Cancers 8 37958406
2022 GEP Tree-Based Prediction Model for Interfacial Bond Strength of Externally Bonded FRP Laminates on Grooves with Concrete Prism. Polymers 8 35631902
2020 Clinical efficacy of 177Lu-DOTATATE peptide receptor radionuclide therapy in thyroglobulin-elevated negative iodine scintigraphy: A "not-so-promising" result compared to GEP-NETs. World journal of nuclear medicine 8 33354174
2018 Development of GP and GEP models to estimate an environmental issue induced by blasting operation. Environmental monitoring and assessment 8 29785545
2016 GEP analysis validates high risk MDS and acute myeloid leukemia post MDS mice models and highlights novel dysregulated pathways. Journal of hematology & oncology 8 26817437
2011 SEOM clinical guidelines for the diagnosis and treatment of gastroenteropancreatic neuroendocrine tumours (GEP NETS). Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico 8 21821488

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