Function of estrogen-related receptor alpha in human endometrial cancer.
BACKGROUND
The estrogen-related receptor alpha (ERRalpha) is an orphan member of the nuclear receptor superfamily that is closely related to estrogen receptor alpha (ERalpha). ERRalpha binds an estrogen response element (ERE), directly competes with ERalpha for binding ERE, and represses ERE-dependent transcription in MCF-7 cells, ER-positive breast cancer cells.


OBJECTIVE
We investigated whether ERRalpha modulate some ER-dependent activities in endometrial cancer.


METHODS
We investigated protein and mRNA expression of ERRalpha in endometrial cancer using immunohistochemistry and RT-PCR, respectively. After transient transfection using the ERRalpha expression vector (pCI-ERRalpha) or ERRalphaSi, which suppressed the expression of endogenous ERRalpha, Ishikawa cells were assayed for ERE-dependent luciferase activity. Cells stably overexpressing ERRalpha were generated and compared with estrogen-dependent and -independent cell growth.


RESULTS
ERRalpha was detected in human endometrial cancer tissues by immunohistochemistry. An RT-PCR study showed that mRNA of ERRalpha was expressed in four endometrial cancer cell lines (Ishikawa, Hec1a, KLE, and SNGII) and 11 human endometrial tissues. Overexpression of ERRalpha repressed estrogen-induced ERE-dependent transcriptional activity in Ishikawa cells. After transfection with ERRalphaSi1, the expression of endogenous ERRalpha decreased to 0.5-fold, and estrogen-induced ERE luciferase activity increased to 1.5-fold. The cells stably overexpressing ERRalpha grew up more slowly than control cells in the presence of 10 nm estradiol.


CONCLUSIONS
ERRalpha is expressed in human endometrial cancer tissues and cell lines and suppresses ERE-dependent transcriptional activity in the presence of estrogen. ERRalpha modulates estrogen-induced activity in estrogen-dependent endometrial cancer.
Watanabe
Ai
A
Department of Obstetrics and Gynecology, Kyoto Prefectural University of Medicine, Kawaramachi Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan.
Kinoshita
Yoshiyuki
Y
Hosokawa
Kenichi
K
Mori
Taisuke
T
Yamaguchi
Takeshi
T
Honjo
Hideo
H
D045744:Cell Line, Tumor; D016889:Endometrial Neoplasms / Q000378:metabolism*; D047628:Estrogen Receptor alpha / Q000502:physiology*; D005260:Female; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D007150:Immunohistochemistry; D008156:Luciferases / Q000235:genetics; D010957:Plasmids / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
D047628:Estrogen Receptor alpha; D012333:RNA, Messenger; D008156:Luciferases; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases