Unknown,Transcriptomics,Genomics,Proteomics

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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. Gene expression profiles from 3T3 cells transformed by SV40 (SV5) and cells expressing both SV40T and wt N-ras (SV5-NN clones) were compared using genome wide mRNA expression profiling by Affymetrix genechip arrays (Mouse 430 2.0) and key targets were validated by real time RT-PCR.

ORGANISM(S): Mus musculus

SUBMITTER: Jiri Zavadil

PROVIDER: E-GEOD-28678 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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

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