title: Wild type N-ras displays anti-malignant properties, in part by downregulating decorin.
abstract: 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.
authors.affiliation: Department of Pathology, New York University School of Medicine, New York, New York, USA. marta.benet@ciberehd.org
authors.forename: Marta
authors.initials: M
authors.lastname: Benet
authors.forename: Robin Yates
authors.initials: RY
authors.lastname: Dulman
authors.forename: Raffi
authors.initials: R
authors.lastname: Suzme
authors.forename: Eleazar Vega-Saenz
authors.initials: EV
authors.lastname: de Miera
authors.forename: Martha E
authors.initials: ME
authors.lastname: Vega
authors.forename: Thuy
authors.initials: T
authors.lastname: Nguyen
authors.forename: Jiri
authors.initials: J
authors.lastname: Zavadil
authors.forename: Angel
authors.initials: A
authors.lastname: Pellicer
mesh_terms: D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics; D002448:Cell Adhesion; D059447:Cell Cycle Checkpoints; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002472:Cell Transformation, Viral / Q000235:genetics; D058575:Decorin / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D011905:Genes, ras; D005838:Genotype; D006801:Humans; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism; D041681:NIH 3T3 Cells; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D000952:Antigens, Polyomavirus Transforming; C546878:DCN protein, human; C546879:Dcn protein, mouse; D058575:Decorin; D035683:MicroRNAs; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta