Phosphatase and tensin homolog gene inhibits the effect induced by gonadotropin-releasing hormone subtypes in human endometrial carcinoma cells.
BACKGROUND
Type I gonadotropin-releasing hormone (GnRH-I) agonists have been applied for the treatment of steroid-dependent tumors such as breast carcinoma, ovarian cancer and prostatic carcinoma. But the mechanism has not been clarified yet. There are few reports about the treatment of endometrial carcinoma using GnRH-I agonists. Type II GnRH (GnRH-II) is a new subtype of GnRH. Our aim was to investigate the effects of GnRH-I agonists and GnRH-II on estrogen receptor-negative human endometrial carcinoma cells and the effect from phosphatase and tensin homolog gene (PTEN) to them.


METHODS
A lentiviral vector-mediated RNAi method was used to establish a PTEN-negative HEC-1A cell clone (HEC-1A-ND). MTT and flow cytometry were used to detect the cell proliferation, cell cycle and apoptosis of HEC-1A, HEC-1A-NC and HEC-1A-ND cells after treatment with GnRH-I agonist Triptorelin (10(-11) mol/L to 10(-5) mol/L) or GnRH-II (10(-11) mol/L to 10(-5) mol/L). Western blotting was used to detect AKT and ERK1/2 activation after treatment with different concentrations of Triptorelin or GnRH-II for 30 minutes in the above mentioned three kinds of cells.


RESULTS
Triptorelin and GnRH-II induced apoptosis and inhibited proliferation of HEC-1A, HEC-1A-ND and HEC-1A-NC in a dose-dependent manner. This effect was augmented in HEC-1A-ND cells in which PTEN gene was knocked-down. Furthermore, Triptorelin and GnRH-II inhibited the AKT and ERK activity in HEC-1A-ND cells.


CONCLUSIONS
Triptorelin and GnRH-II can promote apoptosis rate and inhibit cell proliferation of estrogen receptor-negative endometrial carcinoma cells in a dose-dependent manner. PTEN gene can inhibit the effects of Triptorelin or GnRH-II on human endometrial carcinoma cells.
Zhao
Li-jun
LJ
Department of Obstetrics & Gynecology, Peking University People's Hospital, 100044, Beijing, China.
Liu
Ning
N
Li
Xiao-ping
XP
Wang
Jian-liu
JL
Wei
Li-hui
LH
D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D016889:Endometrial Neoplasms / Q000235:genetics / Q000378:metabolism*; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives / Q000494:pharmacology*; D006801:Humans; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000502:physiology*; D034622:RNA Interference; D017329:Triptorelin Pamoate / Q000494:pharmacology
D017329:Triptorelin Pamoate; D007987:Gonadotropin-Releasing Hormone; C047717:LHRH, His(5)-Trp(7)-Tyr(8)-; D051059:PTEN Phosphohydrolase