PTEN is involved in the signal transduction pathway of contact inhibition in endometrial cells.
PTEN is involved in the regulation of normal cellular functions in addition to its well-known role as a tumor suppressor. In the present study, we have shown that stable transfection of the PTEN gene into PTEN-mutated endometrial carcinoma cells leads to contact inhibition accompanied by a decreased level of phosphorylated-Akt (p-Akt) expression, an increase in p27(Kip1), and a decrease in beta-catenin. PTEN-induced cells with contact inhibition exhibit G0-G1 cell-cycle arrest, and the Ki-67 labeling index is reduced. These changes are canceled by transfection of a double-stranded short-interfering RNA against the PTEN gene. Normal endometrial stromal cells increase their PTEN expression when reaching confluence; this is followed by changes in the expression of Akt-related proteins in the same way as in tumor cells. These results indicate that PTEN, p-Akt, p27, and beta-catenin are involved in the signal transduction of contact inhibition and suggest that PTEN may, in part, control the proliferation of endometrial carcinoma cells through the induction of contact inhibition.
Uegaki
Kazunori
K
Department of Obstetrics and Gynecology, Tottori University School of Medicine, 3-61 Nishimachi, 683-8504, Yonago, Japan.
Kanamori
Yasunobu
Y
Kigawa
Junzo
J
Kawaguchi
Wakae
W
Kaneko
Ruri
R
Naniwa
Jun
J
Takahashi
Masakuni
M
Shimada
Muneaki
M
Oishi
Tetsuro
T
Itamochi
Hiroaki
H
Terakawa
Naoki
N
D002453:Cell Cycle / Q000502:physiology*; D045744:Cell Line, Tumor; D003260:Contact Inhibition; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D004717:Endometrium / Q000166:cytology / Q000502:physiology*; D005260:Female; D006801:Humans; D051058:Oncogene Protein v-akt / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000502:physiology*; D010766:Phosphorylation; D015398:Signal Transduction; D051176:beta Catenin / Q000378:metabolism
D051176:beta Catenin; D050760:Cyclin-Dependent Kinase Inhibitor p27; D051058:Oncogene Protein v-akt; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human