title: Phosphorylation of estrogen receptor beta at serine 105 is associated with good prognosis in breast cancer.
abstract: Estrogen receptor (ER) action is modulated by posttranslational modifications. Although ERalpha phosphorylation correlates with patient outcome, ERbeta is similarly phosphorylated but its significance in breast cancer has not been addressed. We investigated whether ERbeta that is phosphorylated at serine 105 (S105-ERbeta) is expressed in breast cancer and assessed potential clinical implications of this phosphorylation. Following antibody validation, S105-ERbeta expression was studied in tissue microarrays comprising 108 tamoxifen-resistant and 351 tamoxifen-sensitive cases and analyzed against clinical data. S105-ERbeta regulation in vitro was assessed by Western blot, flow cytometry, and immunofluorescence. Nuclear S105-ERbeta was observed in breast carcinoma and was associated with better survival (Allred score > or =3), even in tamoxifen-resistant cases, and additionally correlated with ERbeta1 and ERbeta2 expression. Distinct S105-ERbeta nuclear speckles were seen in some higher grade tumors. S105-ERbeta levels increased in MCF-7 cells in response to 17beta-estradiol, the ERbeta-specific agonist diarylpropionitrile, and the partial ERbeta-agonist genistein. S105-ERbeta nuclear speckles were also seen in MCF-7 cells and markedly increased in size and number at 24 hours following 17beta-estradiol and, in particular diarylpropionitrile, treatment. These speckles were coexpressed with ERbeta1 and ERbeta2. Presence of S105-ERbeta in breast cancer and association with improved survival, even in endocrine resistant breast tumors suggest S105-ERbeta might be a useful additional prognostic marker in this disease.
authors.affiliation: Leeds Institute of Molecular Medicine, University of Leeds, Leeds, UK.
authors.forename: Werbena
authors.initials: W
authors.lastname: Hamilton-Burke
authors.forename: Louise
authors.initials: L
authors.lastname: Coleman
authors.forename: Michele
authors.initials: M
authors.lastname: Cummings
authors.forename: Caroline A
authors.initials: CA
authors.lastname: Green
authors.forename: Deborah L
authors.initials: DL
authors.lastname: Holliday
authors.forename: Kieran
authors.initials: K
authors.lastname: Horgan
authors.forename: Loaie
authors.initials: L
authors.lastname: Maraqa
authors.forename: Mark B
authors.initials: MB
authors.lastname: Peter
authors.forename: Steven
authors.initials: S
authors.lastname: Pollock
authors.forename: Abeer M
authors.initials: AM
authors.lastname: Shaaban
authors.forename: Laura
authors.initials: L
authors.lastname: Smith
authors.forename: Valerie
authors.initials: V
authors.lastname: Speirs
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D016009:Chi-Square Distribution; D047629:Estrogen Receptor beta / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D010766:Phosphorylation; D011379:Prognosis; D034741:RNA, Small Interfering; D012694:Serine / Q000378:metabolism*; D046888:Tissue Array Analysis
chemical_list: D047629:Estrogen Receptor beta; D034741:RNA, Small Interfering; D012694:Serine