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Does EMT Contribute to Radiation Resistance in Human Breast Cancer?
Annual rept. 1 Aug 2011-31 Jul 2012
OKLAHOMA UNIV OKLAHOMA CITY
Pagination or Media Count:
E-cadherin, is the major adhesion protein associated with epithelial malignancies and loss of E-cadherin expression is diagnostic of EMT in such cells. Loss of E-cadherin plays an important role in breast cancer progression, invasion and metastasis and is used as a prognostic marker for breast cancer. E-cadherin expression is significantly reduced in basal-like and triple negative breast cancers and a higher proportion of E-cadherin aberrations are observed in ER- negative tumors. Interestingly, E-cadherin, has been shown to interact with ER and studies have demonstrated a direct role for ER-alpha in controlling E-cadherin expression, with elimination of ER-alpha from an ER-positive cell line or its reintroduction in an ER-negative context, respectively triggering repression or transcription of E-cadherin. Thus, ER-alpha may represent the prime factor controlling the expression of this gene in breast cancer cells, an idea previously suggested only by indirect evidence. In addition to a number of relational observations, the absence of ER-alpha has been mechanistically linked to E-cadherin suppression and EMT and indirect evidence suggests that re-expression of endogenous ER-alpha is linked to reversion of the invasive breast cancer phenotype. The connection between ER-alpha and E-cadherin, therefore, is complex and requires a detailed investigation. Several studies have associated loss of ER with worse tumor grade, aggressive biologic behavior and highly radioresistant breast cancer. However no studies have as yet clearly defined the role of E-cadherin in governing radiosensitivity and therefore, in this grant we propose to investigate this connection in greater detail.
APPROVED FOR PUBLIC RELEASE