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Research ArticleClinical Studies

ER-α36, a Novel Variant of ER-α, is Expressed in ER-positive and -negative Human Breast Carcinomas

LISA M.J. LEE, JIANG CAO, HAO DENG, PING CHEN, ZORAN GATALICA and ZHAO-YI WANG
Anticancer Research January 2008, 28 (1B) 479-483;
LISA M.J. LEE
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JIANG CAO
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HAO DENG
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PING CHEN
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ZORAN GATALICA
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ZHAO-YI WANG
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  • For correspondence: zywang@creighton.edu
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Abstract

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.

Keywords:
  • Estrogen receptor
  • ER-α36
  • ER-negative breast cancer
  • ER-α66

Footnotes

    • Received September 26, 2007.
    • Revision received November 21, 2007.
    • Accepted December 11, 2007.
  • Copyright© 2008 International Institute of Anticaner Research (Dr. John G. Delinassios), All rights reserved
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Anticancer Research: 28 (1B)
Anticancer Research
Vol. 28, Issue 1B
January-February 2008
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ER-α36, a Novel Variant of ER-α, is Expressed in ER-positive and -negative Human Breast Carcinomas
LISA M.J. LEE, JIANG CAO, HAO DENG, PING CHEN, ZORAN GATALICA, ZHAO-YI WANG
Anticancer Research Jan 2008, 28 (1B) 479-483;

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ER-α36, a Novel Variant of ER-α, is Expressed in ER-positive and -negative Human Breast Carcinomas
LISA M.J. LEE, JIANG CAO, HAO DENG, PING CHEN, ZORAN GATALICA, ZHAO-YI WANG
Anticancer Research Jan 2008, 28 (1B) 479-483;
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