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Oncogene. 2004 Nov 4;23(52):8527-34.

Loss of c-abl facilitates anchorage-independent growth of p53- and RB- deficient primary mouse embryonic fibroblasts.

Author information

1
Laboratory of Molecular Oncology, Osaka Bioscience Institute, 6-2-4 Furuedai, Suita, Osaka 565-0874, Japan.

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.

PMID:
15378021
DOI:
10.1038/sj.onc.1207894
[Indexed for MEDLINE]

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