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

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 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.

• Authors: Kuniaki Ohta, Tetsuo Maruyama, Hiroshi Uchida, Masanori Ono, Takashi Nagashima, Toru Arase, Takashi Kajitani, Hideyuki Oda, Mineto Morita, Yasunori Yoshimura
• Journal: Molecular human reproduction (Mol Hum Reprod) Vol. 14 Issue 1 Pg. 17-22 (Jan 2008) ISSN: 1460-2407 [Electronic] England
• PMID: 18178606 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cyclin-Dependent Kinase Inhibitor p21
• Glycodelin
• Glycoproteins
• PAEP protein, human
• Pregnancy Proteins
• RNA, Small Interfering
• Green Fluorescent Proteins
• Cyclin-Dependent Kinase Inhibitor p27
• Progesterone
• Cyclin-Dependent Kinases

Topics

• Cell Line
• Cell Proliferation (drug effects)
• Cyclin-Dependent Kinase Inhibitor p21 (genetics, metabolism)
• Cyclin-Dependent Kinase Inhibitor p27 (genetics, metabolism)
• Cyclin-Dependent Kinases (antagonists & inhibitors)
• Endometrium (cytology)
• Epithelial Cells (cytology, drug effects, metabolism)
• Female
• Flow Cytometry
• Glycodelin
• Glycoproteins (genetics, metabolism, physiology)
• Green Fluorescent Proteins (genetics, metabolism)
• Humans
• Immunoblotting
• Immunoprecipitation
• Pregnancy Proteins (genetics, metabolism, physiology)
• Progesterone (pharmacology)
• RNA, Small Interfering (genetics)
• Reverse Transcriptase Polymerase Chain Reaction
• S Phase (drug effects, genetics, physiology)