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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2004-11

AUTHORS

Keren Paz, Nicholas D Socci, Erik van Nimwegen, Agnes Viale, James E Darnell

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 approximately 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. More... »

PAGES

8455

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/sj.onc.1207803

DOI

http://dx.doi.org/10.1038/sj.onc.1207803

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1053709272

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/15378015


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