Introduction: The estrogen-related receptor (ERR) is an orphan member of the nuclear receptor superfamily that is closely related to estrogen receptor (ER). ERR binds a estrogen response element (ERE), directly competes with ER for binding ERE and represses ERE-dependent transcription in MCF-7 cells, ER-positive breast cancer cells.

Objective: We investigated Weather ERR modulate some ER-dependent activities in endometrial cancer.

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

Result: ERR was detected in human endometrial cancer tissues by immunohistochemistry. And RT-PCR study showed that mRNA of ERR were expressed in 4 endometrial cancer cell lines (Ishikawa, Hec1a, KLE, SNGII) and 11 human endometrial tissues. Overexpression of ERR repressed estrogen-induced ERE-dependent transcriptional activity in Ishikawa cells. After transfected with ERRSi1, the expression of endogenous ERR decrease to 0.5-fold and estrogen induced ERE luciferase activity increased to 1.5-fold. The cells stably overexpressing ERR grew up more slowly than control cells in the presence of 10 nM estradiol.

Conclusion: ERR is expressed in human endometrial cancer tissues and cell lines and suppress ERE-dependent transcriptional activity in the presence of estrogen. ERR modulates estrogen-induced activity in estrogen dependent endometrial cancer.