EFFECT OF OVEREXPRESSION OF THE SMALL HEAT-SHOCK PROTEIN HSP27 ON THEHEAT AND DRUG SENSITIVITIES OF HUMAN TESTIS TUMOR-CELLS

In contrast to most metastatic cancers, testicular germ cell tumors ar e cured in more than 80% of patients using cisplatin-based combination chemotherapy. Testis tumor cells in vitro retain their sensitivity to chemotherapeutic drugs, radiation, and other stresses, such as heat s hock. saving shown that this is associated with low constitutive level s of heat shock protein (HSP) 27, we determined the effect of overexpr ession of HSP27 on the heat and drug sensitivities of a human testis t umor cell line, 833K. Cells were cotransfected with plasmids containin g a neomycin resistance gene and the full-length human HSP27 gene, and four clones that overexpressed HSP27 by factors of 3.7-38.3-fold comp ared with the parental cells were selected. The overexpressing cells w ere more resistant to heat shock, cisplatin, and doxorubicin, and this was associated with modest increases (17-30%) in population doubling times and a small reduction in the number of S-phase cells. These resu lts suggest that the low constitutive levels of HSP27 in testis tumor cells may contribute to the sensitivity of testicular germ cell tumors to chemotherapy, and that targeting HSP27 may improve response rates in other types of cancer.