title: 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.
authors.affiliation: Department of Obstetrics and Gynecology, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Miyamoto
authors.forename: Akiko
authors.initials: A
authors.lastname: Horiuchi
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Kashima
authors.forename: Akihisa
authors.initials: A
authors.lastname: Suzuki
authors.forename: Tomoko
authors.initials: T
authors.lastname: Yamada
authors.forename: Miyuki
authors.initials: M
authors.lastname: Kurai
authors.forename: Ikuo
authors.initials: I
authors.lastname: Konishi
authors.forename: Tanri
authors.initials: T
authors.lastname: Shiozawa
mesh_terms: D000328:Adult; D000368:Aged; D002277:Carcinoma / Q000378:metabolism*; D044842:Cullin Proteins / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism*; D016889:Endometrial Neoplasms / Q000378:metabolism*; D004717:Endometrium / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D008875:Middle Aged; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D044786:S-Phase Kinase-Associated Proteins / Q000378:metabolism*
chemical_list: C100318:Cullin 1; D044842:Cullin Proteins; D019394:Ki-67 Antigen; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D044786:S-Phase Kinase-Associated Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27