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p53 mutations and tetraploids under r- and K-selection

Oncogene volume 21, pages 3043–3049 (2002)Cite this article

Abstract

Cotransfection of rat embryo fibroblasts with c-myc and activated H-ras oncogenes is one experimental model of the multistep oncogenesis associated with p53 mutations and aneuploidy. Using the model, we found that selection processes, e.g., r- and K-selection, affect emergence of p53 mutants and tetraploids. Culture optimum for logarithmic growth (r-selection) selected p53 mutants as they proliferated rapidly, while in confluent culture (K-selection) tetraploids emerged regardless of the p53 status. Transfection of the mutated p53 gene with dominant negative functions eradicated untransfected cells under both r- and K-selection. However, these p53 mutants can be eradicated under K-selection by cells with normal p53 function and that had been selected under prolonged K-selection. The presence of competitors and the type of selection should determine whether or not p53 mutants and/or tetraploids predominate. These observations strengthen the importance of selection processes in case of cancer.

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Acknowledgements

We thank T Iiri for helpful comments and M Ohara for language assistance. This work was supported in part by grants (to T Motokura) from the Ministry of Education, Science, Technology, Sports and Culture of Japan.

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Author notes

  1. Toru Motokura

    Present address: Department of Hematology and Oncology, Graduate School of Medicine, the University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan

Authors and Affiliations

  1. Department of Internal Medicine, Faculty of Medicine, the University of Tokyo, 3-28-6 Mejirodai, Bunkyo-ku, Tokyo, 112-8688, Japan

    Norio Chikatsu, Yukari Nakamura, Hiroyuki Sato, Toshiro Fujita & Toru Motokura

  2. Advanced Clinical Research Center, Institute of Medical Science, the University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan

    Shigetaka Asano

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  1. Norio Chikatsu
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Correspondence to Toru Motokura.

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Chikatsu, N., Nakamura, Y., Sato, H. et al. p53 mutations and tetraploids under r- and K-selection. Oncogene 21, 3043–3049 (2002). https://doi.org/10.1038/sj.onc.1205413

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