For the Mouse gene set with the same name, see SASAI_RESISTANCE_TO_NEOPLASTIC_TRANSFROMATION

Systematic name M1259
Brief description Genes down-regulated in MEF and REF cells (mouse and rat fibroblasts) but not in TIG3/T cells (human lung fibroblasts expressing TERT [GeneID=7015]) by co-expression of the SV40 early region and the activated HRAS (H-RasV12) [GeneID=3265].
Full description or abstract Normal human diploid fibroblasts (HDFs) are refractory to oncogene-mediated transformations in vitro, compared with rodent fibroblasts. As successful oncogene-mediated transformations of normal HDFs have been reported using the human telomerase catalytic subunit, it has been considered that telomerase activity contributes to the species-specific transformability. However, these transformed HDFs are much less malignant compared with those of rodent cells, suggesting the existence of undefined mechanisms that render HDFs resistant to malignant transformation. Here, cDNA microarray analysis identified caveolin-1 as one of the possible cellular factors involved in such mechanisms. The mitogen-activated protein kinases (MAPK) pathway downregulates Caveolin-1 in rodent fibroblasts, transformed by coexpression of the SV40 early region and activated H-Ras. In contrast, the coexpression of these two oncogenes in HDFs failed to reduce the expression level of Caveolin-1. These results strongly suggest the presence of critical differences in events following the phosphorylation of ERK during the activation process of the MAPK signaling pathway between human and rodent cells, as the ERK protein was similarly phosphorylated in both systems. Furthermore, the small interfering RNA-mediated suppression of Caveolin-1 facilitated the oncogene-mediated transformation of normal HDFs, clearly indicating that the differences in the transformability between human and rodent cells are due, at least in part, to the mechanism responsible for the resistance to Ras-induced Caveolin-1 downregulation in HDFs.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 16832346   Authors: Sasai K,Kakumoto K,Hanafusa H,Akagi T
Exact source Table 1
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Source species Mus musculus
Contributed by Arthur Liberzon (MSigDB Team)
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