Conflicts of Interest: The authors declare no conflict of interest.
Original Research Article
Wild type N-ras displays anti-malignant properties, in part by downregulating decorin†
Article first published online: 24 FEB 2012
Copyright © 2011 Wiley Periodicals, Inc.
Journal of Cellular Physiology
Volume 227, Issue 6, pages 2341–2351, June 2012
How to Cite
Benet, M., Dulman, R. Y., Suzme, R., de Miera, E. V.-S., Vega, M. E., Nguyen, T., Zavadil, J. and Pellicer, A. (2012), Wild type N-ras displays anti-malignant properties, in part by downregulating decorin. J. Cell. Physiol., 227: 2341–2351. doi: 10.1002/jcp.22969
- Issue published online: 24 FEB 2012
- Article first published online: 24 FEB 2012
- Accepted manuscript online: 1 AUG 2011 08:41AM EST
- Manuscript Accepted: 25 JUL 2011
- Manuscript Received: 3 JAN 2011
- NIH. Grant Number: CA36327
Previously, we have shown 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 large T antigen (SV40T). 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 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 (decorin) and miRNAs (mir-29A, let-7b) 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 TGFβ 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 by wt N-ras appear to be different from 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. J. Cell. Physiol. 227: 2341–2351, 2012. © 2011 Wiley Periodicals, Inc.