[Regulatory effect of 17beta-estradiol on expression of orphan nuclear receptor ERRalpha in endometrial carcinoma cell lines].
OBJECTIVE
Estrogen receptor-related receptor alpha (ERRalpha), a member of the subfamily of orphan nuclear receptors, could compete with estrogen receptor alpha (ERalpha) to bind the same target genes and interfere in ER signal pathway. Therefore, it might be associated to the tumorigenesis of endometrial carcinoma. This study was to explore the regulatory effect of 17beta-estradiol (17beta-E(2)) on ERRalpha expression, and to elucidate the relationship between ERRalpha and ER signal pathway in endometrial carcinoma cell lines.


METHODS
ERalpha-positive cell line Ishikawa and ERalpha-negative cell line HEC-IA were treated with different concentrations of 17beta-E(2) (1x10(-10) mol/L, 1x10(-8) mol/L, and 1x10(-6) mol/L) for 24 h and 48 h, respectively. The levels of ERRalpha mRNA and protein were examined by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot. 17beta-E(2) (1x10(-8) mol/L) and complete ER inhibitor ICI182,780 (1x10(-6) mol/L) were given concomitantly to observe the change of ERRalpha expression.


RESULTS
The levels of ERRalpha mRNA and protein in Ishikawa cells were down-regulated after stimulated for 24 h and 48 h by different concentrations of 17beta-E(2). The maximal effect was observed at the concentration of 1x10(-8) mol/L. When 17beta-E(2) and ICI182,780 were given simultaneously to Ishikawa cells, this down-regulation was blocked. However, the level of ERRalpha mRNA, not protein, in HEC-IA cells was up-regulated after stimulated by different concentrations of 17beta-E(2) for 24 h. After stimulated by 17beta-E(2) for 48 h, the level of ERRalpha protein was up-regulated, which could not be blocked by ICI182,780.


CONCLUSIONS
17beta-E(2) can down-regulate the expression of ERRalpha in Ishikawa cells, which is mediated by ERalpha. 17beta-E(2) can up-regulate the expression of ERRalpha in HEC-IA cells, but this regulation cannot be blocked by ICI182,780.
Gao
Min
M
Department of Gynecology, Peopleos Hospital, Peking University, Beijing, 100044, P. R. China.
Sun
Peng-Ming
PM
Zhao
Dan
D
Wang
Jian-Liu
JL
Li
Xiao-Ping
XP
Wei
Li-Hui
LH