Inverse correlation between Skp2 and p27^Kip1 in normal endometrium and endometrial carcinoma

Abstract

Cyclin-dependent-kinase (cdk) inhibitor, p27^Kip1 (p27), has been shown to participate in progestin-induced growth suppression of normal endometrial glands. To analyse the molecular mechanisms regulating p27 protein, we examined immunohistochemical expression of the SCF^Skp2 (Skp1-Cullin-F-box protein) complex factors, i.e. Skp1, Cul1 and Skp2, and compared them with that of p27, steroid receptors and Ki-67. In normal endometrial glands, the expression of Skp2 was observed in the proliferative phase, whereas that of p27 was observed in the secretory phase. Cultured normal endometrial glandular cells showed that progesterone induced the down-regulation of Skp2 along with up-regulation of p27. In endometrial carcinomas, the inverse topological correlation between Skp2 and p27 was evident in 39/66 (59%) cases, and the expression of Skp2 showed a strong correlation with Ki-67. These findings suggest that the expression of SCF^Skp2 complex changes during the menstrual cycle in normal endometrium and the SCF^Skp2 ubiquitin-proteasome pathway may also work in endometrial carcinomas.

Keywords:

• Endometrium
• endometrial carcinoma
• p27
• SCF complex
• Skp2

Acknowledgements

This work was supported in part by Grants-in-Aid for Scientific Research from the Ministry of Education, Science and Culture (No. 06454468 and No. 07807154), Japan.