title: Estrogen-related receptor alpha in human breast carcinoma as a potent prognostic factor.
abstract: Estrogen-related receptor alpha (ERRalpha) was identified as a gene related to estrogen receptor alpha (ERalpha) and belongs to a class of nuclear orphan receptors. ERRalpha binds to estrogen responsive element(s) (ERE) and is considered to be involved in modulation of estrogenic actions. However, biological significance of ERRalpha remains largely unknown. Therefore, we examined the expression of ERRalpha in human breast carcinoma tissues using immunohistochemistry (n = 102) and real-time reverse transcription-PCR (n = 30). ERRalpha immunoreactivity was detected in the nuclei of carcinoma cells in 55% of breast cancers examined, and relative immunoreactivity of ERRalpha was significantly (P = 0.0041) associated with the mRNA level. Significant associations were detected between ERalpha and ERE-containing estrogen-responsive genes, such as pS2 (P < 0.0001) and EBAG9/RCAS1 (P = 0.0214), in breast carcinoma tissues. However, no significant association was detected between ERalpha and pS2 (P = 0.1415) in the ERRalpha-positive cases (n = 56) or between ERalpha and EBAG9/RCAS1 (P = 0.8271) in the ERRalpha-negative group (n = 46). ERRalpha immunoreactivity was significantly associated with an increased risk of recurrence and adverse clinical outcome by both uni- (P = 0.0097 and P = 0.0053, respectively) and multi- (P = 0.0215 and P = 0.0118, respectively) variate analyses. A similar tendency was also detected in the group of breast cancer patients who received tamoxifen therapy after surgery. Results from our study suggest that ERRalpha possibly modulates the expression of ERE-containing estrogen-responsive genes, and ERRalpha immunoreactivity is a potent prognostic factor in human breast carcinoma.
authors.affiliation: Department of Pathology, Tohoku University School of Medicine, Sendai, Japan. t-suzuki@patholo2.med.tohoku.ac.jp
authors.forename: Takashi
authors.initials: T
authors.lastname: Suzuki
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Miki
authors.forename: Takuya
authors.initials: T
authors.lastname: Moriya
authors.forename: Norihiro
authors.initials: N
authors.lastname: Shimada
authors.forename: Takanori
authors.initials: T
authors.lastname: Ishida
authors.forename: Hisashi
authors.initials: H
authors.lastname: Hirakawa
authors.forename: Noriaki
authors.initials: N
authors.lastname: Ohuchi
authors.forename: Hironobu
authors.initials: H
authors.lastname: Sasano
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001141:Aromatase / Q000096:biosynthesis / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D044584:Carcinoma, Ductal / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D003131:Combined Modality Therapy; D047628:Estrogen Receptor alpha; D004967:Estrogens / Q000502:physiology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D011379:Prognosis; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis* / Q000235:genetics; D011960:Receptors, Estrogen / Q000096:biosynthesis* / Q000235:genetics; D013629:Tamoxifen / Q000627:therapeutic use; D000097983:ERRalpha Estrogen-Related Receptor
chemical_list: D001141:Aromatase; D047628:Estrogen Receptor alpha; D004967:Estrogens; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D011960:Receptors, Estrogen; D013629:Tamoxifen; D000097983:ERRalpha Estrogen-Related Receptor