Fellowship to Study the Involvement of Heat Shock Proteins in Drug Resistance in Human Breast Cancer

摘要

Heat shock proteins (hsps) are induced in cells in response to environmental stresses. It has been shown that some breast cancer patients express high levels of hsp27, which may augment the aggressiveness of these tumors and make them more resistant to treatment. The research funded by this fellowship was directed at understanding the regulation of hsp27 toward the development of a useful therapy for inhibiting breast cancer progression. In this our final progress report we demonstrated completion of Task 1 -- the examination of the regulatory mechanisms controlling the expression of hsp27 in breast cancer cells. On Task 2 we examined genes whose expression is associated with hsp27 effects on cellular proliferation: metastatic behavior, and drug resistance. We applied the technique of screening expression microarrays to identify candidate cDNA's which were modulated as a result of hsp27 overexpression and/or drug treatment. Furthermore, we have determined that hsp27's effect on drug resistance involved the inhibition of drug-induced apoptosis. Finally, we completed Task 3, cloning of a hsp27 regulatory factor which interferes with hsp27 expression.