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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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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DOI: https://doi.org/10.1038/sj.onc.1203290
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