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Inhibition of v-Abl transformation by p53 and p19ARF

Oncogene volume 18, pages 7731–7739 (1999)Cite this article

Abstract

Tumorigenesis is a multistep process that involves the activation of oncogenes and the inactivation of tumor suppressor genes. The transforming activity of the v-Abl oncogene of Abelson murine leukemia virus (A-MuLV) in immortal cell lines has been well studied, while the effects of v-Abl in primary fibroblasts are less clear. Here we show that v-Abl causes cell cycle arrest in primary mouse embryonic fibroblasts (MEFs) and elevated levels of both p53 and the cyclin-dependent kinase inhibitor p21Cip. p53−/− or p19ARF−/− MEFs were resistant to v-Abl-induced cell cycle arrest. Although wild-type MEFs were resistant to v-Abl transforming activity, p53−/− or p19ARF−/− MEFs were susceptible. The results indicate that loss of p19ARF and p53 function plays an important role during the transformation of primary cells by v-Abl. We suggest that although v-Abl is a potent oncogene, its full potential transforming activity cannot be realized until the ARF-, and p53-dependent growth inhibitory pathway is disabled. We also show that p53 is not the mediator of v-Abl toxicity in immortal fibroblasts and does not determine the susceptibility of immortal fibroblasts to v-Abl transformation.

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Acknowledgements

The authors thank Charles Sherr, Tyler Jacks, Jean Y Wang and Denise Galloway for providing reagents critical to this work. The work was supported in part by NIH grant PO1 CA75399. F Cong is a Roche fellow and SP Goff is an Investigator of the Howard Hughes Medical Institute.

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Authors and Affiliations

  1. Department of Biological Sciences, Columbia University, New York, 10025, NY, USA

    Feng Cong

  2. Department of Microbiology, Columbia University College of Physicians and Surgeons, New York, 10032, NY, USA

    Kathryn Calame & Stephen P Goff

  3. Department of Biochemistry and Molecular Biophysics, Columbia University College of Physicians and Surgeons, New York, 10032, NY, USA

    Xiaoming Zou, Karen Hinrichs, Kathryn Calame & Stephen P Goff

  4. Howard Hughes Medical Institute, Columbia University College of Physicians and Surgeons, New York, 10032, NY, USA

    Stephen P Goff

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Cong, F., Zou, X., Hinrichs, K. et al. Inhibition of v-Abl transformation by p53 and p19ARF. Oncogene 18, 7731–7739 (1999). https://doi.org/10.1038/sj.onc.1203290

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