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Gene expression profiling of fibroblasts resistant toward oncogene-mediated transformation reveals preferential transcription of negative growth regulators

Oncogene volume 18, pages 5448–5454 (1999)Cite this article

Abstract

The signal-transducing Ras proteins are important driving forces of diverse cellular processes such as proliferation, neoplastic transformation, differentiation and growth inhibition. As a step toward understanding the complex mechanisms underlying cellular responses, gene expression patterns were examined in two phenotypically normal fibroblast lines which differ in their sensitivity toward oncogene-mediated transformation. Suppression subtractive hybridization (SSH) was used to establish a subtracted cDNA library specific for the REF52 cell line which, like normal diploid fibroblasts, is refractory toward neoplastic transformation induced by mutated HRAS oncogenes. In contrast, rat 208F control cells can be efficiently transformed by HRAS. The nucleotide sequence of 549 subtracted cDNA clones (‘REF52 minus 208F’) was determined. We identified 93 preferentially expressed gene fragments in resistant REF52 cells as compared to 208F cells. Seventeen of the 52 known genes (32.6%) are capable of inhibiting cell proliferation or of adversely affecting oncogenic signal transduction pathways. These results suggest that the anti-oncogenic properties of resistant REF52 cells are determined by multiple negative growth regulators. The preneoplastic state expressed in 208F cells is characterized by impairment of unexpectedly redundant control mechanisms. Our results also demonstrate that SSH is a powerful method for identifying specific transcriptional patterns in closely related cell types.

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Acknowledgements

This work was supported by Schweizerischer Nationalfonds and Berliner Krebsgesellschaft (grants to R Schäfer). We thank Dr Earl Ruley for REF52 cells.

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Authors and Affiliations

  1. Laboratory of Molecular Tumour Pathology, Institute of Pathology, Charité, Humboldt University Berlin, Schumannstrasse 20/21, Berlin, D-10117, Germany

    Oleg I Tchernitsa, Johannes Zuber, Christine Sers, Roland Brinckmann & Reinhold Schäfer

  2. Department of Pathology, University of Zürich, Zürich, CH-8091, Switzerland

    Oleg I Tchernitsa, Christine Sers, Susan K Britsch & Reinhold Schäfer

  3. Cardiology Centre, University of Leipzig, Russenstrasse 19, Leipzig, D-04289, Germany

    Volker Adams

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Tchernitsa, O., Zuber, J., Sers, C. et al. Gene expression profiling of fibroblasts resistant toward oncogene-mediated transformation reveals preferential transcription of negative growth regulators. Oncogene 18, 5448–5454 (1999). https://doi.org/10.1038/sj.onc.1202987

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