HEAT-SHOCK PROTEIN EXPRESSION IN CISPLATIN-SENSITIVE AND CISPLATIN-RESISTANT HUMAN TUMOR-CELLS

It has been suggested that the expression of certain heat-shock protei ns (HSPs) may be prognostic markers in several tumor types. Since HSPs may be involved in determining cellular sensitivity to chemotherapeut ic drugs, the possible relation between HSP expression and cisplatin ( cDDP) sensitivity was studied. Three human germ-cell tumor cell lines, human small-cell lung carcinoma (SCLC) cell line and 3 human colon ca rcinoma cell lines were used as a model for differences in intrinsic c DDP sensitivity. The constitutive expression of a panel of HSPs was st udied by immunoblotting. No correlation was found between expression o f HSP90, HSP73, HSP72, HSP60 and HSP27 and the extent of intrinsic cDD P sensitivity when all cell lines studied were considered. However, fo r the 3 cell lines derived from germ-cell carcinomas, HSP27 expression was inversely related to cDDP sensitivity; i.e. decreased HSP27 level s were associated with decreased sensitivity. Constitutive HSP express ion was also studied in 2 sets of human cell lines with in vitro acqui red cDDP resistance. In both resistant cell lines, decreased expressio n of HSP27 (as determined by Western blotting) was found as compared t o the sensitive parent cell lines. Thus, acquired resistance to cDDP w as also accompanied by decreased HSP27 expression. Interestingly, when basal HSP27 mRNA levels were measured in the SCLC cell line (GLC(4)) and its subline with acquired resistance (GLC(4)-cDDP), no significant differences were detected. Continuous cDDP incubation increased HSP27 levels and induced HSP27 phosphorylation in GLC(4) cells, but not in the resistant subline. Thus, although no general relationships between HSP expression and cDDP sensitivity are apparent, high HSP27 expressi on in vitro relates to high sensitivity to cDDP treatment in some tumo r types. This is in accordance with reported clinical data on high HSP 27 levels in tumors correlating with good prognosis.