Effect of staurosporine on the transcription of HSP70 heat shock gene in HT-29 cells.
We have investigated the effects of staurosporine (STP), an inhibitor of PKC, on the expression of the HSP70 gene in human colon carcinoma HT-29 cells. Cells were heated at 45 degrees C for 15 min and incubated at 37 degrees C for up to 6 hr with or without STP. When STP (5 micrograms/ml) was added during 37 degrees C incubation, the accumulation of HSP70 mRNA was suppressed. The suppression of the mRNA accumulation was due to the decrease in initiation and elongation activity of the HSP70 gene. Our study also demonstrated that the effect of STP on the elongation and accumulation of HSP70 mRNA appeared to be selective and the drug did not influence the elongation and accumulation of the house keeping gene, beta-actin mRNA. In addition, the drug did not alter the early response of heat shock gene expression, the heat-induced HSF binding activity. These results suggest that STP affects the late response of the transcriptional regulatory system of HSP genes.
Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI 48073.
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D000199:Actins / Q000096:biosynthesis; D000470:Alkaloids / Q000494:pharmacology*; D015152:Blotting, Northern; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D003110:Colonic Neoplasms; D015342:DNA Probes; D015870:Gene Expression / Q000187:drug effects*; D006360:Heat-Shock Proteins / Q000096:biosynthesis*; D006801:Humans; D007700:Kinetics; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D019311:Staurosporine; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects*; D014407:Tumor Cells, Cultured
D000199:Actins; D000470:Alkaloids; D015342:DNA Probes; D006360:Heat-Shock Proteins; D012333:RNA, Messenger; D011493:Protein Kinase C; D019311:Staurosporine