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Wild type N-ras displays anti-malignant properties, in part by downregulating decorin

ABSTRACT: Previously, we have demonstrated that wild type N-ras (wt N-ras) harbors an anti-malignant effect against mutated Ras and in tumors without Ras mutations. To investigate the molecular bases of this anti-malignant activity, we have studied the potency of this anti-malignant effect in a model system against SV40 T. We show that wild-type N-ras (wt N-ras) counteracts the effects of SV40T in NIH3T3 cells as seen by a decrease in proliferation, anchorage independence and changes in migration). We also show that wt N-ras also elicits the same anti-malignant effects in some human tumor cell lines (HT1080 and MDA-MB-231). Through mRNA and microRNA (miRNAs) expression profiling we have identified genes and miRNAs modulated by wt N-ras potentially responsible for the anti-malignant effect. wt N-ras appears to mediate its anti-malignant effect by downregulating some of the targets of the TGFb pathway and decorin, which are able to reverse the inhibition of migration induced by wt N-ras. Our experiments show that the molecules that mediate the anti-malignant effect appear to be different than those modulated by transforming N-ras. The components of the pathways modulated by wt N-ras mediating its anti-malignant effects are potential targets for therapeutic intervention in cancer. We report that the N-ras proto-oncogene has anti-malignant effects and that it does so by modulating different genes than its oncogenic counterpart, which indicates that it should be activating different pathways.

ORGANISM(S): Mus musculus

PROVIDER: GSE28678 | GEO | 2011/04/19

SECONDARY ACCESSION(S): PRJNA138933

REPOSITORIES: GEO

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Wild type N-ras displays anti-malignant properties, in part by downregulating decorin

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