title: Estrogen-related receptor γ modulates cell proliferation and estrogen signaling in breast cancer.
abstract: Breast cancer is primarily a hormone-dependent tumor that can be regulated by status of steroid hormones including estrogen and progesterone. Estrogen-related receptors (ERRs) are orphan nuclear receptors most closely related to estrogen receptor (ER) and much attention has been recently paid to the functions of ERRs in breast cancer in terms of the interactions with ER. In the present study, we investigated the expression of ERRγ in human invasive breast cancers by immunohistochemical analysis (n=110) obtained by radical mastectomy. Nuclear immunoreactivity of ERRγ was detected in 87 cases (79%) and tended to correlate with the lymph node status. No significant associations were observed with other clinicopathological characteristics, including the expression levels of both estrogen and progesterone receptors. In MCF-7 breast cancer cells, we demonstrated that ERRγ mRNA was up-regulated dose-dependently by estrogen, and that this up-regulation of ERRγ mRNA by estrogen was abolished by ICI 182,780 treatment. We also demonstrated that exogenously transfected ERRγ increased MCF-7 cell proliferation. Furthermore, ERRγ enhanced estrogen response element (ERE)-driven transcription in MCF-7 cells. In 293T cells, ERRγ could also stimulate ERE-mediated transcription with or without ERα. These results suggest that ERRγ plays an important role as a modulator of estrogen signaling in breast cancer cells.
authors.affiliation: Division of Gene Regulation and Signal Transduction, Research Center for Genomic Medicine, Saitama Medical University, Saitama, Japan.
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Ijichi
authors.forename: Takashi
authors.initials: T
authors.lastname: Shigekawa
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Ikeda
authors.forename: Kuniko
authors.initials: K
authors.lastname: Horie-Inoue
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Fujimura
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Tsuda
authors.forename: Akihiko
authors.initials: A
authors.lastname: Osaki
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Saeki
authors.forename: Satoshi
authors.initials: S
authors.lastname: Inoue
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014162:Transfection; D015854:Up-Regulation
chemical_list: C490917:ESRRG protein, human; D004967:Estrogens; D012333:RNA, Messenger; D011960:Receptors, Estrogen