THE SMALL HEAT-SHOCK PROTEIN HSP27 IS CORRELATED WITH GROWTH AND DRUG-RESISTANCE IN HUMAN BREAST-CANCER CELL-LINES

An emerging body of evidence suggests that the heat shock proteins (hs p) may be involved in drug resistance. When hsp are induced by elevate d temperatures, resistance to doxorubicin (Dox), but not to other comm only used chemotherapeutic agents, is induced in breast cancer cells. To evaluate the role of hsp27 in this phenomenon, we have transfected MDA-MB-231 breast cancer cells, which normally express low levels of h sp27, with a full-length hsp27 construct. These hsp27-overexpressing c ells now display a 3-fold elevated resistance to Dox. Anchorage-depend ent proliferation and anchorage-independent growth were also increased 2-4-fold in these transfectants. We have also derived a MCF-7 breast cancer cell line with amplified endogenous hsp27 which is highly resis tant to Dox. When these cells are transfected with an antisense hsp27 construct, they are rendered sensitive to Dox (3-fold) with anchorage- dependent as well as anchorage-independent growth, similarly decreased . These results suggest that hsp27 specifically confers Dox resistance in human breast cancer cells and, furthermore, that hsp27 may be invo lved in the regulation of cell growth.