The Role of Estrogen Receptor-Alpha in Breast Cancer Metastases to Bone
Final rept. 1 Sep 1999-31 Aug 2002
TEXAS UNIV HEALTH SCIENCE CENTER AT SANANTONIO
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Breast cancer osteolysis is common and the morbidity is devastating. The consequences of intractable bone pain, fracture, hypercalcemia and nerve compression syndromes are debilitating and the tumor is incurable once it has metastasized to bone. Women with bone metastases live many years with this incurable complication and are at high risk for morbidity. A more aggressive approach to prevent and treat bone metastases is a necessary addition to the standard armamentarium for breast cancer therapy in order to impact on this morbidity. Although bisphosphonates are now FDA-approved for treatment of established bone metastases and have had significant impact on bone pain and fracture, considerable advances are necessary for the eventual prevention or reversal of bone metastases. These data indicate a role for TGFbeta to potentiate ER-alpha -mediated transcription induced by a constitutively active ER-alpha. The above in vitro studies provide rationale for targeting the downstream effects of TGFbeta on breast cancer cells to treat and eventually prevent osteolysis. However, in vivo, expression of wild-type ER-alpha and mutants Ser47Thr, Lys531Glu, and Tyr537Asn had no effect on bone metastases in a mouse model. Thus, further experiments to test the in vivo relevance of these in vitro findings are warranted.
- Medicine and Medical Research