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Transformation fingerprint: induced STAT3-C, v-Src and Ha-Ras cause small initial changes but similar established profiles in mRNA

Oncogene volume 23, pages 8455–8463 (2004)Cite this article

Abstract

Induced transformation of mouse fibroblasts was carried out by releasing tetracycline-repressed expression of an oncogenic mutant of STAT3, STAT3-C, or of v-Src or Ha-Ras. At 15 days after derepression of each oncogene, DNA microarrays showed elevation (>3-fold) of a similar group of ∼25 mRNAs compared to untransformed cells. RT–PCR confirmed a number of these mRNA elevations. RNA samples were then analysed at intervals during the first 24 h after doxycycline removal to determine the time of early changes. Extensive changes were not observed by array analysis, except in v-Src-expressing cells where about 10 mRNAs were elevated threefold or more. However, RT–PCR did uncover changes in each derepressed cell type that included some of the changes observed after the 15-day transformation period. In addition, STAT3-C target genes such as BclXI and cyclin D1, which were not observed on array analysis, were elevated by RT–PCR analysis. We conclude, therefore, that early after oncogene induction, transcriptional changes, including those initiated by STAT3-C, may occur only in scarce mRNA and/or to a limited extent. However, with additional time and probably additional cell division, a new epigenetic state is established that is mirrored by a changed transcriptional profile emblematic of transformation by each of three oncogenes.

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Acknowledgements

This work was supported by NIH grants AI32489 and AI34420 to JED. KP is a Human Frontier Science Program fellow. We thank Lois Cousseau for assistance with manuscript preparation.

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Authors and Affiliations

  1. Laboratory of Molecular Cell Biology, The Rockefeller University, 1230 York Avenue, New York, 10021, NY, USA

    Keren Paz & James E Darnell

  2. Department of Pathology, Albert Einstein College of Medicine, Bronx, 10461, NY, USA

    Nicholas D Socci

  3. Center for Studies in Physics and Biology, The Rockefeller University, New York, 10021, NY, USA

    Erik van Nimwegen

  4. Memorial Sloan-Kettering Cancer Center, New York, 10021, NY, USA

    Agnes Viale

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  1. Keren Paz
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  2. Nicholas D Socci
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Correspondence to James E Darnell.

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Supplementary Information accompanies the paper on Oncogene website (http://www.nature.com/onc).

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Paz, K., Socci, N., van Nimwegen, E. et al. Transformation fingerprint: induced STAT3-C, v-Src and Ha-Ras cause small initial changes but similar established profiles in mRNA. Oncogene 23, 8455–8463 (2004). https://doi.org/10.1038/sj.onc.1207803

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