ER-alpha36, a novel variant of ER-alpha, is expressed in ER-positive and -negative human breast carcinomas.
BACKGROUND
The status of estrogen receptor-alpha (ER-alpha) expression is one of the most important diagnostic and prognostic factors of breast cancer. ER-alpha 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-alpha, ER-alpha36, which lacks both transactivation domains and functions as a dominant-negative effector of transactivation activities of the full-length ER-alpha (ER-alpha66) and ER-beta. ER-alpha36 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-alpha36 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-alpha36 may play important roles in breast cancer tumorigenesis, it is of clinical importance to examine the expression pattern of ER-alpha36, in addition to that of ER-alpha66, for more comprehensive molecular profiling of breast carcinomas.


METHODS
Thirty-one breast cancer patient tissues were evaluated for ER-alpha36 and ER-alpha66 protein expression status by IHC and six additional patient tissue samples were analyzed by Western blot analysis using antibodies specific to ER-alpha66 or ER-alpha36.


RESULTS
Our experiments reveal a cytoplasmic and plasma-membrane-associated expression pattern of ER-alpha36 in both ER-alpha66-positive and -negative breast cancer samples. Furthermore, ER-alpha36 expression appears to be associated with decreasing nuclear and/or cytoplasmic ER-alpha66 expression, suggesting its potential use as a diagnostic and prognostic marker.


CONCLUSIONS
ER-alpha36 is a novel isoform of ER-alpha, frequently expressed in ER-alpha66-negative cancers, whose detection may provide additional information for better diagnosis and prognosis.
Lee
Lisa M J
LM
Department of Pathology, Creighton University Medical School, Omaha, NE 68178, USA.
Cao
Jiang
J
Deng
Hao
H
Chen
Ping
P
Gatalica
Zoran
Z
Wang
Zhao-Yi
ZY
D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D047628:Estrogen Receptor alpha / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D020033:Protein Isoforms
D047628:Estrogen Receptor alpha; D020033:Protein Isoforms