Mol. Hum. Reprod. Advance Access originally published online on June 25, 2004
Molecular Human Reproduction 2004 10(8):567-572; doi:10.1093/molehr/gah084
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Decreased level of the cell cycle regulator p27 and increased level of its ubiquitin ligase Skp2 in endometrial carcinoma but not in normal secretory or in hyperstimulated endometrium
1Departments of Obstetrics and Gynecology and 2Department of Pathology, Carmel Medical Center, Haifa, 3Department of Pathology, Rambam Medical Center and 4Department of Biochemistry, The Bruce Rappaport Faculty of Medicine and the Rappaport Family Institute for Research in the Medical Science, Technion–Israel Institute of Technology, Haifa, Israel
5 To whom correspondence should be addressed at: Dr Shirly Lahav-Baratz, Carmel Medical Center, 7 Michal Street, 34362 Haifa, Israel. Email: lahav{at}adi.org.il
p27 is a cyclin-dependent kinase (CDK) inhibitor whose specific late G1 destruction allows progression of the cell across the G1/S boundary. The protein is ubiquitinated by S-phase kinase-interacting protein-2 (Skp2) following its specific phosphorylation, and is subsequently degraded by the 26s proteasome. There is a direct relationship between low level of p27 and rapid proliferation occurring in several benign states and in many malignancies. In the glandular cells of the normal endometrium, the level of p27 is exceedingly low during the proliferative phase, whereas it is markedly increased during the secretory phase. The expression of p27 in endometrial carcinoma is very low but has been found to increase following treatment with progesterone. However, estrogen exposure is considered as a major risk factor in developing endometrial cancer. The implications of the high dose of estrogen and progesterone induced during IVF treatment are still unknown. We have examined the expression of p27 and Skp2 as well as of Ki67 proliferation marker by using endometrial extracts and cells from normal endometrium, from ovarian hyperstimulated patients, and from endometrial carcinoma patients. The expression of p27, Skp2 and Ki67 was found to be similar in both normal secretory endometrium and endometrium from ovarian hyperstimulated patients. In striking contrast, p27 is significantly lower while Skp2 and Ki67 are significantly higher in the endometrial carcinoma and in endometrium from the proliferative phase compared with their normal secretory counterpart tissue.
Key words: endometrium/IVF/ovarian hyperstimulation/p27/ubiquitin
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