Effect of overexpression of the small heat shock protein HSP27 on the heat and drug sensitivities of human testis tumor cells.
In contrast to most metastatic cancers, testicular germ cell tumors are 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 shock. Having shown that this is associated with low constitutive levels of heat shock protein (HSP) 27, we determined the effect of overexpression of HSP27 on the heat and drug sensitivities of a human testis tumor cell line, 833K. Cells were cotransfected with plasmids containing 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 compared with the parental cells were selected. The overexpressing cells were 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 results 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.
Richards
E H
EH
Institute of Urology and Nephrology, University College London, United Kingdom.
Hickey
E
E
Weber
L
L
Master
J R
JR
D001692:Biological Transport; D002455:Cell Division; D002945:Cisplatin / Q000378:metabolism / Q000494:pharmacology; D004249:DNA Damage; D004261:DNA Replication / Q000187:drug effects; D004273:DNA, Neoplasm / Q000032:analysis; D004317:Doxorubicin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006360:Heat-Shock Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D006358:Hot Temperature; D006801:Humans; D008297:Male; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis*; D013736:Testicular Neoplasms / Q000473:pathology*; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000187:drug effects
D004273:DNA, Neoplasm; D006360:Heat-Shock Proteins; D011993:Recombinant Fusion Proteins; D004317:Doxorubicin; D002945:Cisplatin