ER-alpha36, a novel variant of ER-alpha, is expressed in ER-positive and -negative human breast carcinomas

Anticancer Res. 2008 Jan-Feb;28(1B):479-83.

Abstract

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.

Patients and 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.

Conclusion: 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Breast Neoplasms / metabolism*
  • Cell Membrane / metabolism
  • Cytoplasm / metabolism
  • Estrogen Receptor alpha / biosynthesis*
  • Humans
  • Immunohistochemistry
  • Protein Isoforms

Substances

  • Estrogen Receptor alpha
  • Protein Isoforms