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A genetic screen to identify genes that rescue the slow growth phenotype of c-myc null fibroblasts

Oncogene volume 19, pages 3330–3334 (2000)Cite this article

Abstract

The c-myc gene is frequently over-expressed in human cancers and is involved in regulation of proliferation, differentiation and apoptosis. c-Myc is a transcription factor that acts primarily by regulating the expression of other genes. However, it has been very difficult to identify bona fide c-Myc target genes that explain its diverse biological activities. The recent generation of c-myc deficient Rat1A fibroblasts with a profound and stable growth defect provides a new system to search for genes that can substitute for c-myc in proliferation. In this study, we have attempted to identify genes that rescue the slow growth phenotype of c-myc null cells through introduction of a series of potent cell cycle regulatory genes and several retroviral cDNA expression libraries. None of the candidate genes tested, including SV40 T-antigen and adenovirus E1A, caused reversal of the c-myc null growth defect. Furthermore, extensive screens with high-complexity retroviral cDNA libraries from three different tissue sources revealed that only c-myc and N-myc rescued the c-myc null slow-growth phenotype. Our data support the notion that there are no functional equivalents of the myc family of proto-oncogenes and also suggest that there are no c-Myc-activated genes that alone can substitute for c-Myc in control of cell proliferation.

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Acknowledgements

We thank J Sedivy for the kind gift of the myc null cells, Drs B Amati, AJ van der Eb, W Krek, D Peeper and M van Lohuizen for the gift of plasmids and antisera. This work was supported by the Dutch Cancer Society (KWF) and a Biomed 2 program grant from the European Community to R Bernards and by grants from the Edward Mallinckrodt, Jr. Foundation and NCI CA76418-01 to GQ Daley.

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Authors and Affiliations

  1. Division of Molecular Carcinogenesis, and Center for Biomedical Genetics, The Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam, 1066, CX, The Netherlands

    Katrien Berns, E Marielle Hijmans & René Bernards

  2. Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, 02142, Massachusetts, MA, USA

    Eugene Koh & George Q Daley

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  1. Katrien Berns
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Berns, K., Hijmans, E., Koh, E. et al. A genetic screen to identify genes that rescue the slow growth phenotype of c-myc null fibroblasts. Oncogene 19, 3330–3334 (2000). https://doi.org/10.1038/sj.onc.1203639

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