Abstract
The c-abl tyrosine kinase is the proto-oncogene of the v-abl oncogene of the Abelson murine leukemia virus. Although mutational variants of c-Abl can exhibit gain of function and can produce a transformed phenotype, the function of c-Abl in transformation remained unclear. Here, we report that the loss of c-abl facilitates transformation. c-abl-knockout mouse embryonic fibroblasts (MEFs) immortalized by SV40 T antigen acquired anchorage-independent growth, and by constructing mutational variants of T antigen we showed that binding of large T antigen to p53 and RB was necessary to induce anchorage-independent growth. Although c-abl/p53 double-knockout MEFs did not undergo anchorage-independent growth, those expressing human papilloma virus 16 E7, which mainly inactivates RB, did. Our results show that the loss of c-abl facilitates anchorage-independent growth in the context of p53 and RB deficiency, and suggest that loss of function of c-abl facilitates some types of transformation.
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Acknowledgements
We thank Ian Smith for critically reading our manuscript. We acknowledge Makiko Maeda and Toshie Terada for technical assistance. We are also grateful to Masuo Yutsudo, Toshio Kitamura, David Baltimore, Richard Mulligan, Stephan Feller, Sharon Boast and Feng Cong for reagents and help. T Shishido was a domestic research fellow of the Japan Science and Technology Corporation and the Japan Society for the Promotion of Science. This work was supported by a specially promoted research grant and a Grant-in-Aid for 21st Century COE Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan, as well as a fund from Ono Pharmaceutical Co., Ltd. T Shishido was also supported by Osaka Cancer Research Foundation.
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Suzuki, J., Sukezane, T., Akagi, T. et al. Loss of c-abl facilitates anchorage-independent growth of p53- and RB- deficient primary mouse embryonic fibroblasts. Oncogene 23, 8527–8534 (2004). https://doi.org/10.1038/sj.onc.1207894
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DOI: https://doi.org/10.1038/sj.onc.1207894
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