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Cooperation of oncogenic K-ras and p53 deficiency in pleomorphic rhabdomyosarcoma development in adult mice

Oncogene volume 25, pages 7673–7679 (2006)Cite this article

Abstract

Human rhabdomyosarcomas (RMSs) frequently demonstrate genetic alterations in ras and p53. To investigate their possible involvement in the tumorigenesis, we generated a knock-in mouse line with oncogenic K-ras, conditionally expressed by Cre/LoxP system on a background of p53 alteration. Electroporation of Cre expression vector in skeletal muscle tissues resulted in the generation of tumor in adults with tumor incidences of 100% at 10 weeks and 40% at 15 weeks, in p53−/− and p53−/+ backgrounds, respectively. The tumor histology was pleomorphic RMS with characteristic bizarre giant cells, positive for desmin and α-sarcomeric actin and exhibiting remarkable increase in total and phosphorylated extracellular signal-regulated protein kinase (ERK)1 and ERK2. Loss of the wild-type p53 was detected in K-rasG12V-expressed tumors of p53−/+ mice. Early lesions 3 weeks after electroporation consisted of proliferating populations of myogenic progenitors, including stem cells positive for ScaI antigen, immature cells positive for desmin and neural cell adhesion molecule-positive myotubes. Thus, cooperation of oncogenic K-ras and p53 deficiency resulted in the development of pleomorphic RMS in adult mice, providing a useful mouse model for further detailed studies.

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Acknowledgements

We thank Mr Otake for his excellent assistance in animal generation and maintenance. We are grateful to Dr Morita and Dr Shiraishi for their special help in histological preparation.

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Authors and Affiliations

  1. Department of Animal Genomics, Functional Genomics Institute, Mie University Life Science Research Center, Tsu, Mie, Japan

    H Tsumura, H Saito & N Suzuki

  2. Pathology and Matrix Biology, Mie University Graduate School of Medicine, Tsu, Mie, Japan

    T Yoshida & K Imanaka-Yoshida

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  1. H Tsumura
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  2. T Yoshida
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  3. H Saito
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  4. K Imanaka-Yoshida
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  5. N Suzuki
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Correspondence to N Suzuki.

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Tsumura, H., Yoshida, T., Saito, H. et al. Cooperation of oncogenic K-ras and p53 deficiency in pleomorphic rhabdomyosarcoma development in adult mice. Oncogene 25, 7673–7679 (2006). https://doi.org/10.1038/sj.onc.1209749

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