TOREMIFENE, A NOVEL ANTIESTROGEN, CAN OVERCOME HSP27-INDUCED DRUG-RESISTANCE IN HUMAN BREAST-CANCER CELLS

Human breast cancer cell lines derived from MDA-MB-231 were constructe d to express hsp27 constitutively. The elevated presence of this prote in resulted in an enhanced ability to survive a heat shock and exposur e to doxorubicin, a chemotherapeutic agent. Hsp27 expression was unabl e to protect cells from doxorubicin if they were cultured in the prese nce of to remifene. Flow cytometry analysis indicated that cells expos ed to both toremifene and doxorubicin accumulate at G2 + M. Protective effects of hsp27 were overcome by addition of an estrogen antagonist at clinically nontoxic levels. Addition of toremifene to chemotherapeu tic regimes may enhance the sensitivity of breast cancer cells to doxo rubicin.