ArticleEndocrinology2012
GATA4 is a critical regulator of gonadectomy-induced adrenocortical tumorigenesis in mice.
Article in Endocrinology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 25 citations in OpenAlex.
- Transgenic Mouse Models to Study the Development and Maintenance of the Adrenal Cortex.International journal of molecular sciences · 2022Review
- Effect of Inactivation ofJournal of the Endocrine Society · 2022Article
- Genetic variations in the transcription factorsDrug design, development and therapy · 2019Article
- Steroidogenic differentiation and PKA signaling are programmed by histone methyltransferase EZH2 in the adrenal cortex.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Probing GATA factor function in mouse Leydig cells via testicular injection of adenoviral vectors.Reproduction (Cambridge, England) · 2017Article
- GATA4 Regulates Blood-Testis Barrier Function and Lactate Metabolism in Mouse Sertoli Cells.Endocrinology · 2016Article
- GATA factors in endocrine neoplasia.Molecular and cellular endocrinology · 2016Review
- Mouse models of adrenocortical tumors.Molecular and cellular endocrinology · 2016Review
- Toying with fate: Redirecting the differentiation of adrenocortical progenitor cells into gonadal-like tissue.Molecular and cellular endocrinology · 2015Review
- GATA4 is a key regulator of steroidogenesis and glycolysis in mouse Leydig cells.Endocrinology · 2015Article
- Novel markers of gonadectomy-induced adrenocortical neoplasia in the mouse and ferret.Molecular and cellular endocrinology · 2015Article
- GATA4 immunolocalization in breast carcinoma as a potent prognostic predictor.Cancer science · 2014Article
- Laser capture microdissection-reduced representation bisulfite sequencing (LCM-RRBS) maps changes in DNA methylation associated with gonadectomy-induced adrenocortical neoplasia in the mouse.Nucleic acids research · 2013Article
- Conditional mutagenesis of Gata6 in SF1-positive cells causes gonadal-like differentiation in the adrenal cortex of mice.Endocrinology · 2013Article
- Transgenic GATA-4 expression induces adrenocortical tumorigenesis in C57Bl/6 mice.Journal of cell science · 2013Article
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Authors and funding
12 authors at 4 institutions in 3 countries.
Funding
Abstract
In response to gonadectomy certain inbred mouse strains develop sex steroidogenic adrenocortical neoplasms. One of the hallmarks of neoplastic transformation is expression of GATA4, a transcription factor normally present in gonadal but not adrenal steroidogenic cells of the adult mouse. To show that GATA4 directly modulates adrenocortical tumorigenesis and is not merely a marker of gonadal-like differentiation in the neoplasms, we studied mice with germline or conditional loss-of-function mutations in the Gata4 gene. Germline Gata4 haploinsufficiency was associated with attenuated tumor growth and reduced expression of sex steroidogenic genes in the adrenal glands of ovariectomized B6D2F1 and B6AF1 mice. At 12 months after ovariectomy, wild-type B6D2F1 mice had biochemical and histological evidence of adrenocortical estrogen production, whereas Gata4(+/-) B6D2F1 mice did not. Germline Gata4 haploinsufficiency exacerbated the secondary phenotype of postovariectomy obesity in B6D2F1 mice, presumably by limiting ectopic estrogen production in the adrenal glands. Amhr2-cre-mediated deletion of floxed Gata4 (Gata4(F)) in nascent adrenocortical neoplasms of ovariectomized B6.129 mice reduced tumor growth and the expression of gonadal-like markers in a Gata4(F) dose-dependent manner. We conclude that GATA4 is a key modifier of gonadectomy-induced adrenocortical neoplasia, postovariectomy obesity, and sex steroidogenic cell differentiation.
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