Transcription factors GATA-4 and GATA-6 and a GATA family cofactor, FOG-2, are expressed in human ovary and sex cord-derived ovarian tumors

• Published in: The journal of clinical endocrinology and metabolism Vol. 85; no. 9; pp. 3476 - 3483
• Main Authors: LAITINEN, Mika P. E, ANTTONEN, Mikko, KETOLA, Ilkka, WILSON, David B, RITVOS, Olli, BUTZOW, Ralf, HEIKINHEIMO, Markku
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Endocrine Society 01.09.2000
• Subjects: Adult; Aged; Biological and medical sciences; Blotting, Southern; Cells, Cultured; Cloning, Molecular; Corpus Luteum - cytology; Corpus Luteum - metabolism; DNA Probes; DNA-Binding Proteins - biosynthesis; DNA-Binding Proteins - genetics; Female; Female genital diseases; GATA4 Transcription Factor; GATA6 Transcription Factor; Gene Expression Regulation, Neoplastic - genetics; Granulosa Cells - metabolism; Gynecology. Andrology. Obstetrics; Humans; Immunohistochemistry; In Situ Hybridization; Medical sciences; Middle Aged; Ovarian Neoplasms - metabolism; Ovary - metabolism; Reverse Transcriptase Polymerase Chain Reaction; RNA, Neoplasm - biosynthesis; RNA, Neoplasm - genetics; Sex Cord-Gonadal Stromal Tumors - metabolism; Transcription Factors - biosynthesis; Transcription Factors - genetics; Tumors; Zinc Fingers; Human; Immunohistochemistry; Theca folliculi; Pathogenesis; Gene expression; Female genital diseases; Pathology; Ovarian diseases; Ovary; Development; Female; Tumor; Granulosa; Transcription factor; Ovarian follicle
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.85.9.3476

Previous studies have implicated transcription factors GATA-4 and GATA-6 in the regulation of murine ovarian development and function. In rodents, GATA-4 is expressed in granulosa cells of primary and early antral follicles, whereas GATA-6 is expressed in granulosa cells of late antral follicles and luteal glands. Both transcription factors can be detected in lesser amounts in theca cells and interstitial cells. We have now examined the expression of GATA-4 and GATA-6 in human ovaries, human granulosa-luteal (GL) cells and sex cord-derived tumors. We show by in situ hybridization and immunohistochemistry that GATA-4 and GATA-6 messenger RNA (mRNA) and GATA-4 protein are present in granulosa and theca cells in both preantral and antral follicles. Both human ovarian tissue samples and freshly isolated GL cells derived from preovulatory follicles of gonadotropin-treated women express GATA-4, GATA-6, and FOG-2 transcripts, and GATA-6 mRNA expression in GL cell cultures is stimulated by human CG and 8-bromo-cAMP. The vast majority of granulosa and theca cell tumors examined expressed GATA-4 and GATA-6. We also found that mRNA for FOG-2, a recently discovered regulator of GATA-4, is coexpressed with GATA-4 in human ovary samples, normal granulosa cells, and in sex cord-derived tumors. Our results demonstrate that GATA-4, GATA-6, and FOG-2 are expressed in human ovary and in granulosa and theca cell tumors. Our findings support a role for GATA-binding proteins in human ovarian folliculogenesis. Moreover, these data suggest that GATA factors may contribute to the phenotypes of sex cord-derived ovarian tumors.