TY - JOUR T1 - ER-α36, a Novel Variant of ER-α, is Expressed in ER-positive and -negative Human Breast Carcinomas JF - Anticancer Research JO - Anticancer Res SP - 479 LP - 483 VL - 28 IS - 1B AU - LISA M.J. LEE AU - JIANG CAO AU - HAO DENG AU - PING CHEN AU - ZORAN GATALICA AU - ZHAO-YI WANG Y1 - 2008/01/01 UR - http://ar.iiarjournals.org/content/28/1B/479.abstract N2 - Background: The status of estrogen receptor-alpha (ER-α) expression is one of the most important diagnostic and prognostic factors of breast cancer. ER-α is a 66-kDa, ligand-induced transcription factor, characteristically detected in the cell nucleus by immunohistochemistry (IHC) in breast cancer specimens. Recently, we identified and cloned a 36-kDa novel variant of ER-α, ER-α36, which lacks both transactivation domains and functions as a dominant-negative effector of transactivation activities of the full-length ER-α (ER-α66) and ER-β. ER-α36 primarily localizes to the cytoplasm and plasma membrane, and responds to both estrogens and antiestrogens by transducing membrane-initiated signaling cascades, stimulating proliferation and possibly contributing to a more aggressive phenotype in breast carcinomas. ER-α36 is expressed in established ER-positive and -negative breast cancer cell lines. However, its expression and localization in breast cancer specimens have not been evaluated. As ER-α36 may play important roles in breast cancer tumorigenesis, it is of clinical importance to examine the expression pattern of ER-α36, in addition to that of ER-α66, for more comprehensive molecular profiling of breast carcinomas. Patients and Methods: Thirty-one breast cancer patient tissues were evaluated for ER-α36 and ER-α66 protein expression status by IHC and six additional patient tissue samples were analyzed by Western blot analysis using antibodies specific to ER-α66 or ER-α36. Results: Our experiments reveal a cytoplasmic and plasma-membrane-associated expression pattern of ER-α36 in both ER-α66-positive and -negative breast cancer samples. Furthermore, ER-α36 expression appears to be associated with decreasing nuclear and/or cytoplasmic ER-α66 expression, suggesting its potential use as a diagnostic and prognostic marker. Conclusion: ER-α36 is a novel isoform of ER-α, frequently expressed in ER-α66-negative cancers, whose detection may provide additional information for better diagnosis and prognosis. ER -