RGD Reference Report - 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.

General

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.
Authors:	Lahav-Baratz, S Ben-Izhak, O Sabo, E Ben-Eliezer, S Lavie, O Ishai, D Ciechanover, A Dirnfeld, M
Citation:	Lahav-Baratz S, etal., Mol Hum Reprod. 2004 Aug;10(8):567-72. Epub 2004 Jun 25.
RGD ID:	2315045
Pubmed:	PMID:15220466 (View Abstract at PubMed)
DOI:	DOI:10.1093/molehr/gah084 (Journal Full-text)
p27 is a cyclin-dependent kinase (CDK) inhibitor whose specific late G(1) destruction allows progression of the cell across the G(1)/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.

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Term	Qualifier	Evidence	With	Reference	Notes	Source	Original Reference(s)
Endometrial Neoplasms		IEP		2315045		RGD
Endometrial Neoplasms		ISO	SKP2 (Homo sapiens)	2315045; 2315045		RGD

Objects Annotated

Genes (Rattus norvegicus)

Skp2 (S-phase kinase associated protein 2)

Genes (Mus musculus)

Skp2 (S-phase kinase-associated protein 2)

Genes (Homo sapiens)

SKP2 (S-phase kinase associated protein 2)

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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.