Human Gene Set: STANHILL_HRAS_TRANSFROMATION_UP


Standard name STANHILL_HRAS_TRANSFROMATION_UP
Systematic name M1265
Brief description Selected genes up-regulated in Rat1Ras cells (fibroblasts) which were transformed by expression of an oncogenic activated form of HRAS [GeneID=3265] compared to the parental Rat1 cells.
Full description or abstract Heat shock proteins (Hsps) are overexpressed in many tumors, but are downregulated in some tumors. To check for a direct effect of Ha-Ras(val12) 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-Ras(val12) induced this promoter. Promoter analysis via systematic deletions and point mutations revealed that Ha-Ras(val12) induces HSP70b transcription via heat shock elements (HSEs). Also, Ha-Ras(val12) induction of HSE-mediated transcription was dramatically reduced in HSF1-/- cells. Yet, residual effect of Ha-Ras(val12) that was still measured in HSF1-/- cells suggests that some of the Ha-Ras(val12) effect is Hsf1-independent. When HSF1-/- cells, stably expressing Ha-Ras(val12), were grown on soft agar only small colonies were formed suggesting a role for heat shock factor 1 (Hsf1) in Ha-Ras(val12)-mediated transformation. Although Ha-ras(Val12) seems to be an inducer of HSP70's expression, we found that in Ha-ras(Val12-)transformed fibroblasts expression of this gene is suppressed. This suppression is correlated with higher sensitivity of Ha-ras(val12)-transformed cells to heat shock. We suggest that Ha-ras(Val12) 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.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 16278678   Authors: Stanhill A,Levin V,Hendel A,Shachar I,Kazanov D,Arber N,Kaminski N,Engelberg D
Exact source Table 1
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Source species Rattus norvegicus
Contributed by Leona Saunders (MSigDB Team)
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identifier namespace		 RAT_SEQ_ACCESSION
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Version history 2022.1.Hs: Reintroduced after previously being screened out by mapping thresholds.

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