Glycodelin blocks progression to S phase and inhibits cell growth: a possible progesterone-induced regulator for endometrial epithelial cell growth

Molecular Human Reproduction
Kuniaki OhtaYasunori Yoshimura

Abstract

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 ...Continue Reading

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Citations

Nov 13, 2008·Histochemistry and Cell Biology·Christiane Kunert-KeilMichael Kasper
Mar 1, 2011·Trends in Endocrinology and Metabolism : TEM·Shujie YangKimberly K Leslie
Aug 23, 2008·International Journal of Cancer. Journal International Du Cancer·Laura C HautalaHannu Koistinen
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Dec 15, 2017·Frontiers in Immunology·Juan CuiXiuwen Wang
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Mar 14, 2013·Reproductive Medicine and Biology·Hiroshi UchidaYasunori Yoshimura
Sep 15, 2016·Oncology Letters·Alexandra C KölblUlrich Andergassen
Mar 25, 2020·Laboratory Investigation; a Journal of Technical Methods and Pathology·Laura C HautalaHannu Koistinen

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