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Essential Role for Ras Signaling in Glioblastoma Maintenance

¹ Molecular Medicine and Virology Group and ² Laboratory of Cell Signaling and Carcinogenesis, Van Andel Research Institute, Grand Rapids, Michigan

Requests for reprints: Sheri L. Holmen, Molecular Medicine and Virology Group, Van Andel Research Institute, 333 Bostwick Avenue, Northeast Grand Rapids, MI 49503. Phone: 616-234-5516; Fax: 616-234-5517; E-mail: sheri.holmen{at}vai.org.

Malignant gliomas can be induced in mice through the combined expression of activated forms of both KRas and Akt in glial progenitor cells. To determine the reliance of these tumors on continued KRas signaling in vivo, we generated a viral vector that allows the expression of KRas to be controlled post-delivery. Tumor-free survival rates were compared between those animals with continued KRas expression and animals in which KRas expression was suppressed. KRas signaling was found to be required for the maintenance of these tumors in vivo; inhibition of KRas expression resulted in apoptotic tumor regression and increased survival. Subsequent reexpression of KRas reinitiated tumor growth, indicating that a percentage of the progenitor cells survived and retained tumorigenic properties.

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