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

Authors

  • Marta Benet,

    Corresponding author
    1. Department of Pathology, New York University School of Medicine, New York, New York
    Current affiliation:
    1. Unidad de Hepatología Experimental CIBERehd, Centro de Investigación, Hospital Universitario La Fe, Valencia, Spain.
    • Unidad de Hepatología Experimental CIBERehd, Centro de Investigación, Hospital Universitario La Fe, Valencia, Spain.
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  • Robin Yates Dulman,

    1. Department of Pathology, New York University School of Medicine, New York, New York
    2. Department of Pediatrics, New York University School of Medicine, New York, New York
    Current affiliation:
    1. Inova Fairfax hospital, 8505 Arlington blvd, Fairfax, VA 22031.
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  • Raffi Suzme,

    1. Department of Pathology, New York University School of Medicine, New York, New York
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  • Eleazar Vega-Saenz de Miera,

    1. Department of Pathology, New York University School of Medicine, New York, New York
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  • Martha E. Vega,

    1. Department of Pathology, New York University School of Medicine, New York, New York
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  • Thuy Nguyen,

    1. Department of Pathology, New York University School of Medicine, New York, New York
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  • Jiri Zavadil,

    1. Department of Pathology, New York University School of Medicine, New York, New York
    2. NYU Genome Technology Center, New York
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  • Angel Pellicer

    1. Department of Pathology, New York University School of Medicine, New York, New York
    Current affiliation:
    1. Department of Pathology New York University School of Medicine, 550 First Avenue, New York, NY 10016.
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  • Conflicts of Interest: The authors declare no conflict of interest.

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. J. Cell. Physiol. 227: 2341–2351, 2012. © 2011 Wiley Periodicals, Inc.

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