An estrogen receptor alpha-dependent regulation of estrogen receptor-related receptor alpha in the proliferation of endometrial carcinoma cells.

Abstract

Estrogen receptor-related receptor alpha (ERRalpha) was reported to compete with estrogen receptor alpha (ERalpha) in a constitutive manner as an orphan nuclear closely related to (ERalpha). To discuss the role of ERRalpha in the endometrial carcinoma cells, this study was performed. ER-responsive endometrial carcinoma cells Ishikawa and ER-nonresponse HEC-1A cells were treated with different concentration of 17beta-E2 or E2 plus ICI 182780. Semiquantitative reverse transcription-polymerase chain reaction and western blot were performed to analysis the expression of human estrogen receptor-related receptor alpha (hERRalpha). Plasmid PLXSN-hERRalpha was constructed and transfected into cells. Selected in the medium containing high-dose G418, the Ishikawa and HEC-1A cells with stable overexpression of hERRalpha were constructed and renamed as Ishikawa/hERRalpha and HEC-1A/hERRalpha, respectively. To discuss the effect of overexpression of hERRalpha in the cell biological behavior (3-[4,5-dimethylth-lazol-2yl]-2,5-diphenyltetrazolium bromid) (MTT) cell assay was performed. Estrogen downregulates ERRalpha expression in ER-positive Ishikawa cells, while upregulates the expression of ERRalpha in ER-negative HEC-1A cells. In Ishikawa cells, the downregulation of 17beta-E2 in ERRalpha expression cells could be blocked by ICI 182780. A decreasing expression of hERalpha was observed in the ER-responsive cells with overexpression of ERRalpha (Ishikawa/hERRalpha). Overexpression of hERRalpha inhibits the cell proliferation in the ERalpha-responsive Ishikawa cells and stimulated the cell proliferation in the ERalpha-nonresponsive HEC-1A cells. Function of hERRalpha depends on the expression and function of hERalpha. ER-mediated signaling might be the important factor resulting in the hormone-dependent endometrial carcinoma, whereas ERRalpha-mediated pathway might act as the vital role in hormone-independent endometrial carcinoma.

• Authors: P-M Sun, M Gao, L-H Wei, A Mustea, J-L Wang, D Könsgen, W Lichtenegger, J Sehouli
• Journal: International journal of gynecological cancer : official journal of the International Gynecological Cancer Society (Int J Gynecol Cancer) Vol. 16 Suppl 2 Pg. 564-8 ( 2006) ISSN: 1048-891X [Print] England
• PMID: 17010074 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• ERRalpha estrogen-related receptor
• Estrogen Receptor alpha
• Estrogen Receptor beta
• Receptors, Estrogen

Topics

• Blotting, Western
• Cell Proliferation
• Endometrial Neoplasms (metabolism)
• Estrogen Receptor alpha (genetics, metabolism)
• Estrogen Receptor beta (genetics, metabolism)
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Receptors, Estrogen (metabolism)
• Tumor Cells, Cultured