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Ha-rasval12 induces HSP70b transcription via the HSE/HSF1 system, but HSP70b expression is suppressed in Ha-rasval12-transformed cells

Oncogene volume 25, pages 1485–1495 (2006)Cite this article

Abstract

Heat shock proteins (Hsps) are overexpressed in many tumors, but are downregulated in some tumors. To check for a direct effect of Ha-Rasval12 on HSP70 transcription, we transiently expressed the oncoprotein in Rat1 fibroblasts and monitored its effect on HSP70b promoter-driven reporter gene. We show that expression of Ha-Rasval12 induced this promoter. Promoter analysis via systematic deletions and point mutations revealed that Ha-Rasval12 induces HSP70b transcription via heat shock elements (HSEs). Also, Ha-Rasval12 induction of HSE-mediated transcription was dramatically reduced in HSF1−/− cells. Yet, residual effect of Ha-Rasval12 that was still measured in HSF1−/− cells suggests that some of the Ha-Rasval12 effect is Hsf1-independent. When HSF1−/− cells, stably expressing Ha-Rasval12, were grown on soft agar only small colonies were formed suggesting a role for heat shock factor 1 (Hsf1) in Ha-Rasval12-mediated transformation. Although Ha-rasVal12 seems to be an inducer of HSP70's expression, we found that in Ha-rasVal12-transformed fibroblasts expression of this gene is suppressed. This suppression is correlated with higher sensitivity of Ha-rasval12-transformed cells to heat shock. We suggest that Ha-rasVal12 is involved in Hsf1 activation, thereby inducing the cellular protective response. Cells that repress this response are perhaps those that acquire the capability to further proliferate and become transformed clones.

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Acknowledgements

We thank, Nadav Askari, Eran Blachinsky, Ruth Cohen, Melanie Grably, Irit Marbach and Gilad Yaakov for useful discussions. The study was supported by the ABISCH-FRENKEL foundation (to AS) and by the Israel Science Foundation, Grant 548/01 (to DE).

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Authors and Affiliations

  1. Department of Biological Chemistry, The Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel

    A Stanhill, V Levin, A Hendel & D Engelberg

  2. Department of Functional Genomics, Sheba Medical Center, Tel-Hashomer, Israel

    I Shachar

  3. GI Oncology Unit and Department of Gastroenterology, Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

    D Kazanov & N Arber

  4. University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    N Kaminski

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  1. A Stanhill
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Correspondence to D Engelberg.

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Stanhill, A., Levin, V., Hendel, A. et al. Ha-rasval12 induces HSP70b transcription via the HSE/HSF1 system, but HSP70b expression is suppressed in Ha-rasval12-transformed cells. Oncogene 25, 1485–1495 (2006). https://doi.org/10.1038/sj.onc.1209193

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