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

Tsutomu Miyamoto1, Akiko Horiuchi, Hiroyasu Kashima

  • 1Department of Obstetrics and Gynecology, Shinshu University School of Medicine, Matsumoto, Japan.

Gynecological Endocrinology : the Official Journal of the International Society of Gynecological Endocrinology
|September 3, 2009
PubMed

Insights

The SCF(Skp2) complex regulates p27 protein levels in the endometrium. Its expression changes with the menstrual cycle and may be involved in endometrial cancer progression.

Area of Science:

  • Gynecologic Oncology
  • Cellular and Molecular Biology
  • Endocrinology

Background:

  • p27(Kip1) (p27) is a cyclin-dependent kinase inhibitor involved in progestin-induced growth suppression in normal endometrial glands.
  • The SCF(Skp2) complex, comprising Skp1, Cullin1, and Skp2, is a key regulator of p27 protein degradation via the ubiquitin-proteasome pathway.

Purpose of the Study:

  • To investigate the molecular mechanisms regulating p27 protein expression in the endometrium.
  • To analyze the expression of SCF(Skp2) complex factors (Skp1, Cul1, Skp2) in relation to p27, steroid receptors, and Ki-67 in normal and cancerous endometrial tissues.

Main Methods:

  • Immunohistochemical analysis of Skp1, Cul1, Skp2, p27, steroid receptors, and Ki-67 expression.
  • Examination of cultured normal endometrial glandular cells treated with progesterone.

Main Results:

  • In normal endometrium, Skp2 expression peaked in the proliferative phase, while p27 expression was highest in the secretory phase.
  • Progesterone treatment of cultured endometrial cells led to decreased Skp2 and increased p27 expression.
  • An inverse correlation between Skp2 and p27 expression was observed in 59% of endometrial carcinomas.
  • Skp2 expression strongly correlated with Ki-67, a marker of cell proliferation, in endometrial carcinomas.

Conclusions:

  • SCF(Skp2) complex expression exhibits dynamic changes throughout the menstrual cycle in normal endometrium.
  • The SCF(Skp2) ubiquitin-proteasome pathway is implicated in the regulation of p27 and may play a role in the pathogenesis of endometrial carcinomas.

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