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Negative regulation of Par-4 by oncogenic Ras is essential for cellular transformation

Oncogene volume 18, pages 7115–7123 (1999)Cite this article

Abstract

Oncogenic variants of the cellular Ras protein are often associated with different types of human cancers. However, the mechanisms by which oncogenic Ras induces transformation are not fully established. Expression of the transcriptional repressor Par-4 was down-regulated by oncogenic Ras via the Raf – MEK – ERK pathway. Restoration of Par-4 levels by abrogation of the Raf – MEK – ERK pathway with the MEK-inhibitor PD98059 or by ectopic Par-4, that acted to inhibit ERK expression and activation, was sufficient to suppress oncogenic Ras-induced transformation. These findings identify Par-4 as a novel target that has to be down-modulated by oncogenic Ras for successful transformation.

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Acknowledgements

This work was supported by the NIH Grant R01 CA60872 (to VM Rangnekar).

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Authors and Affiliations

  1. Department of Surgery, University of Kentucky, Lexington, Kentucky, KY 40536, USA,

    Shirley Guofang Qiu, Sumathi Krishnan & Vivek M Rangnekar

  2. 40536, Kentucky, KY, USA

    Shirley Guofang Qiu, Sumathi Krishnan & Vivek M Rangnekar

  3. Microbiology and Immunology, University of Kentucky, Lexington, 40536, Kentucky, KY, USA

    Nadia El-Guendy & Vivek M Rangnekar

  4. LP Markey Cancer Center, University of Kentucky, Lexington, 40536, Kentucky, KY, USA

    Vivek M Rangnekar

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  1. Shirley Guofang Qiu
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  4. Vivek M Rangnekar
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Qiu, S., Krishnan, S., El-Guendy, N. et al. Negative regulation of Par-4 by oncogenic Ras is essential for cellular transformation. Oncogene 18, 7115–7123 (1999). https://doi.org/10.1038/sj.onc.1203199

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