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Wild type N‐ras displays anti‐malignant properties, in part by downregulating decorin
Author(s) -
Benet Marta,
Dulman Robin Yates,
Suzme Raffi,
de Miera Eleazar VegaSaenz,
Vega Martha E.,
Nguyen Thuy,
Zavadil Jiri,
Pellicer Angel
Publication year - 2012
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.22969
Subject(s) - decorin , cancer research , ht1080 , microrna , oncogene , biology , wild type , microbiology and biotechnology , gene , chemistry , cell cycle , mutant , biochemistry , tumor cells , extracellular matrix , proteoglycan
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.