Glycodelin blocks progression to S phase and inhibits cell growth: a possible progesterone-induced regulator for endometrial epithelial cell growth.
Glycodelin blocks progression to S phase and inhibits cell growth: a possible progesterone-induced regulator for endometrial epithelial cell growth.
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DOI：
10.1093/molehr/gam081
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发表时间：
2008
影响因子：
4
通讯作者：
Kuniaki Ohta;T. Maruyama;H. Uchida;M. Ono;T. Nagashima;T. Arase;Takashi Kajitani;H. Oda;M. Morita;Y. Yoshimura
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文献类型：
--
作者：
Kuniaki Ohta;T. Maruyama;H. Uchida;M. Ono;T. Nagashima;T. Arase;Takashi Kajitani;H. Oda;M. Morita;Y. Yoshimura
长期暴露于无对抗性雌激素而无孕激素可引起子宫内膜增生和癌。排卵后孕酮对子宫内膜上皮细胞（EECs）的正常生长和分化是必需的。孕激素暴露诱导子宫内膜产生许多生物活性物质，其中之一是糖蛋白glycodelin（Gd）。我们研究了Gd在细胞周期进程和细胞生长中的作用，以更好地了解Gd如何影响EEC行为和子宫内膜癌的发病机制。将编码增强型绿色荧光蛋白（EGFP）或EGFP融合Gd（EGFP-Gd）的表达质粒转染分化良好的人子宫内膜上皮癌细胞系石川细胞。然后对它们进行细胞增殖测定、流式细胞术细胞周期分析和包括p21、p27和p16的细胞周期蛋白依赖性激酶抑制剂（CDKIs）的RT-PCR分析。EGFP-Gd的过表达导致细胞增殖活性降低，G1期细胞聚集，p21、p27和p16 mRNA表达上调。此外，通过使用siRNA敲除Gd，部分减弱了炔雌醇诱导的石川细胞生长抑制。这些结果表明Gd引起G1/S进程的抑制以及CDKI的上调，从而降低细胞生长。因此，孕酮诱导的Gd表达可能，至少部分地，有助于抑制子宫内膜上皮细胞的生长在分泌期观察。
Prolonged exposure to unopposed estrogen in the absence of progesterone gives rise to endometrial hyperplasia and carcinoma. Post-ovulatory progesterone is necessary for the proper growth and differentiation of endometrial epithelial cells (EECs). Progesterone exposure induces the endometrial production of numerous bioactive substances, one of which is the glycoprotein, glycodelin (Gd). We investigated the role of Gd in cell cycle progression and cell growth to better understand how Gd affects EEC behavior and endometrial cancer pathogenesis. Ishikawa cells, a well-differentiated human endometrial epithelial cancer cell line, were transfected with expression plasmids encoding enhanced green fluorescent protein (EGFP) or EGFP-fused Gd (EGFP-Gd). They were then subjected to a cell proliferation assay, flow cytometry cell cycle analysis and RT-PCR analysis of cyclin-dependent kinase inhibitors (CDKIs) including p21, p27 and p16. Overexpression of EGFP-Gd resulted in a reduction of cell proliferation activity, an accumulation of G1-phase cells and up-regulation of p21, p27 and p16 mRNAs. Furthermore, progesterone-induced inhibition of Ishikawa cell growth was partially attenuated by Gd knockdown using siRNA. These results indicate that Gd causes inhibition of G1/S progression together with up-regulation of CDKIs thereby reducing cell growth. Thus, progesterone-induced expression of Gd may, at least in part, contribute to the suppression of endometrial epithelial growth observed during the secretory phase.