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Expression of a down-regulated target, SSeCKS, reverses v-Jun-induced transformation of 10T1/2 murine fibroblasts

Oncogene volume 20, pages 141–146 (2001)Cite this article

Abstract

Line 10T1/2 mouse fibroblast overexpressing the v-Jun oncoprotein were morphologically altered, grew into multilayered foci in culture and formed colonies when suspended in agar. The growth rate of the v-Jun-transformed 10T1/2 cells was not changed significantly from that of the untransformed parental cells, but the saturation density of the transformed cultures exceeded that of normal controls by a factor of 2. mRNA extracted from v-Jun-transformed 10T1/2 cells was analysed for differential gene expression with DNA micro-array technology. One of the targets downregulated by v-Jun was identified as SSeCKS (Src-suppressed C kinase substrate). Re-expression of SSeCKS in v-Jun-transformed fibroblasts reversed the transformed phenotype of the cells. Their ability to form foci was reduced to background levels, the number and size of agar colonies was lowered by a factor of 10 and the saturation density was significantly diminished. However, expression of SSeCKS had little effect on the morphology of v-Jun-transformed 10T1/2 cells. These data suggest that the SSeCKS protein has growth-attenuating properties. Down-regulation of SSeCKS may be essential for Jun-induced transformation.

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Acknowledgements

This work was supported by grant CA42564 from the National Cancer Institute; S Cohen is the recipient of a fellowship from NIH training grant 5 T32 DK07022, and A Waha is supported by the Deutsche Forschungsgemeinschaft (WA1428/1-1). The p-Babe-puro vector and PA317, BOSC23 and 10T1/2 cells were a gift from Edward Stavnezer (Department of Biochemistry, Case Western Reserve University). The p53−/− and Rb−/− mouse embryo fibroblasts were a gift from Tyler Jacks (Department of Biology, Massachusetts Institute of Technology). This is manuscript number 13353-MEM at The Scripps Research Institute.

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  1. Gen-Probe Incorporated, 10210 Genetic Center Drive, San Diego, 92121, California CA, USA

    Steven B Cohen

  2. Department of Molecular and Experimental Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, 92037, California CA, USA

    Anke Waha & Peter K Vogt

  3. Department of Microbiology, Mount Sinai School of Medicine, New York, 10029-6574, NY, USA

    Iwin H Gelman

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Cohen, S., Waha, A., Gelman, I. et al. Expression of a down-regulated target, SSeCKS, reverses v-Jun-induced transformation of 10T1/2 murine fibroblasts. Oncogene 20, 141–146 (2001). https://doi.org/10.1038/sj.onc.1204077

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