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
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
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DOI：
10.1210/jc.85.9.3476
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发表时间：
2000-09-01
影响因子：
5.8
通讯作者：
Heikinheimo, M
中科院分区：
文献类型：
--
作者：
Laitinen, MPE;Anttonen, M;Heikinheimo, M
以往的研究表明，转录因子GATA-4和GATA-6参与了小鼠卵巢发育和功能的调节。在啮齿动物中，GATA-4在初级和有腔卵泡的颗粒细胞中表达，而GATA-6在有腔卵泡晚期和黄体腺的颗粒细胞中表达。这两种转录因子都可以在膜细胞和间质细胞中检测到少量。我们现在已经检测了GATA-4和GATA-6在人卵巢、人颗粒-黄体(GL)细胞和性索来源肿瘤中的表达。原位杂交和免疫组织化学结果显示，GATA-4和GATA-6信使RNA(MRNA)和GATA-4蛋白均存在于腔前卵泡和腔前卵泡的颗粒细胞和膜细胞中。人卵巢组织样本和新鲜分离的GL细胞均表达GATA-4、GATA-6和FOG-2转录本，人CG和8-溴-cAMP可刺激GL细胞培养中GATA-6mRNA的表达。绝大多数颗粒细胞和卵泡膜细胞肿瘤表达GATA-4和GATA-6。我们还发现，最近发现的GATA-4的调节因子FOG-2的mRNA与GATA-4在人卵巢样本、正常颗粒细胞和性索来源的肿瘤中共同表达。我们的结果表明，GATA-4、GATA-6和FOG-2在人卵巢、颗粒细胞和卵泡膜细胞瘤中都有表达。我们的发现支持GATA结合蛋白在人类卵泡发生中的作用。此外，这些数据表明GATA因子可能与性索来源的卵巢肿瘤的表型有关。
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.