Hsp27 overexpression inhibits doxorubicin-induced apoptosis in human breast cancer cells

Previously we demonstrated that heat shock protein 27 (hsp27) overexpressio n confers resistance to the chemotherapeutic agent doxorubicin in MDA-MB-23 1 breast cancer cells. Since induction of apoptosis is one underlying mecha nism of chemotherapeutic drug action, we investigated the effect of hsp27 o verexpression on doxorubicin-induced apoptosis, finding that hsp27 protects MDA-MB-231 cells from apoptosis. We also examined expression of the doxoru bicin target, topoisomerase II (topo II), in control and hsp27-overexpressi ng stable transfectants, as topo II expression is important for both drug s ensitivity and the initiation of apoptosis by doxorubicin. The relative lev els of both topo II alpha and beta were higher in the controls than the hsp 27-overexpressing clones, suggesting that the apoptotic protective effect o f hsp27 overexpression in MDA-MB-231 cells is associated with altered topo II expression.abstract