Silencing HSF1 by short hairpin RNA decreases cell proliferation and enhances sensitivity to hyperthermia in human melanoma cell lines

Background: Heat shock transcription factor 1 (HSF1) is a major transactivator of genes coding for heat shock proteins (Hsps). Recent studies demonstrate that HSF1 is involved in tumor initiation, maintenance, and progression by regulating the expression of Hsps and other molecular targets. However, the role of HSF1 in melanoma is largely unknown. Objective: The aim of this study is to analyze the role of HSF1 in melanoma. Methods: We used short hairpin RNA (shRNA) to silence HSF1 in the human melanoma MeWo cell line and investigated its effect on cell proliferation and in the efficacy of chemotherapy, hyperthermia and thermochemotherapy. Results: We found that proliferation of MeWo cells treated with HSF1 shRNA was markedly reduced, and this was associated with a G(1) block of the cell cycle, whereas HSF1 shRNA treatment of normal human keratinocyte HaCat cells had no effect on proliferation. Suppression of cell proliferation by silencing HSF1 was also observed in other melanoma cell lines, HMV-I and HMV-II. Furthermore, silencing HSF1 enhanced the sensitivity of MeWo cells to heat shock, yet did not affect their sensitivity to treatment with dacarbazine. Conclusion: These findings show that HSF1 is required for normal growth and survival of melanoma cells under heat shock conditions, and suggests that HSF1 is a promising therapeutic target in melanoma. (C) 2010 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.