Heat shock protein 70 is required for the survival of cancer cells.
The major stress-inducible heat shock protein, Hsp70, is a chaperone protein abundantly and preferentially expressed in human tumors and tumor cell lines. Owing to the ability of Hsp70 to protect cells from a wide range of apoptotic and necrotic stimuli, it has been assumed that Hsp70 may confer survival advantage to tumor cells. To investigate this hypothesis in human tumor cell lines, we generated an adenovirus expressing antisense Hsp70 (Ad.asHsp70). The effective and specific depletion of Hsp70 by Ad.asHsp70 resulted in massive cell death of all tumorigenic cell lines tested (carcinomas of breast, colon, prostate and liver as well as glioblastoma). In spite of an effective depletion of Hsp70, Ad.asHsp70 had no effect on the survival or growth of fetal fibroblasts or non-tumorigenic epithelial cells of breast or prostate. Anti-apoptotic proteins Bcl-2, Bcl-XL and CrmA as well as peptide-inhibitors of caspases, DEVD-CHO and zVAD-FMK, failed to rescue tumor cells from Ad.asHsp70-induced cell death. These results indicate that the high expression of Hsp70 is a prerequisite for the survival of human cancer cells of various origins and reveal Hsp70 as the only protein described so far whose expression is specifically needed for the survival of tumorigenic cells.
Nylandsted
J
J
Apoptosis Laboratory, Institute of Cancer Biology, Danish Cancer Society, DK-2100 Copenhagen Ø, Denmark.
Brand
K
K
Jäättelä
M
M
D000256:Adenoviridae / Q000235:genetics; D016375:Antisense Elements (Genetics); D017209:Apoptosis / Q000502:physiology*; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival; D005822:Genetic Vectors; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D020287:In Situ Nick-End Labeling; D009369:Neoplasms / Q000473:pathology*; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
D016375:Antisense Elements (Genetics); D018840:HSP70 Heat-Shock Proteins; D020169:Caspases