ER-alpha36, a novel variant of ER-alpha, is expressed in ER-positive and -negative human breast carcinomas
Lee, L.M.J.; Cao, J.; Deng, H.; Chen, P.; Gatalica, Z.; Wang, Z-Yi.
Anticancer Research 28(1b): 479-483
2008
ISSN/ISBN: 0250-7005 PMID: 18383888 Document Number: 617037
Background: The status of estrogen receptor-alpha (ER-a) expression is one of the most important diagnostic and prognostic factors of breast cancer. ER-alpha is a 66-kDa, ligand-induced transcription factor, characteristical detected in the cell nucleus by imnumohistochemistry (IHC) in breast cancer specimens. Recently, we identified and cloned a 36-kDa novel variant of ER-a, ER-alpha 36, which lacks both transactivation domains and functions as a dominant-negative effector of transactivation activities of the full-length ER-a (ER-alpha 66) and ER-P. ER-alpha 36 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-alpha 36 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-alpha 36 may play important roles in breast cancer tumorigenesis, it is of clinical importance to examine the expression pattern of ER-alpha 36, in addition to that of ER-a66, for more comprehensive molecular profiling of breast carcinomas. Patients and Methods: Thirty-one breast cancer patient tissues were evaluated for ER-a36 and ER-alpha 66 protein expression status by IHC and six additional patient tissue samples were analyzed by Western blot analysis using antibodies specific to ER-alpha 66 or ER-alpha 36. Results: Our experiments reveal a cytoplasmic and plasma-membrane-associated expression pattern of ER-alpha 36 in both ER-alpha 66-positive and -negative breast cancer samples. Furthermore, ER-alpha 36 expression appears to be associated with decreasing nuclear and/or cytoplasmic ER-alpha 66 expression, suggesting its potential use as a diagnostic and prognostic marker. Conclusion: ER-alpha 36 is a novel isoform of ER-a, frequently expressed in ER-alpha 66-negative cancers, whose detection may provide additional information for better diagnosis and prognosis.