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

Oncogene. 2004 Nov 4;23(52):8455-63. doi: 10.1038/sj.onc.1207803.

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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Transformation, Neoplastic / metabolism
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Gene Expression Profiling
  • Gene Expression Regulation / physiology
  • Mice
  • Oncogene Protein pp60(v-src) / genetics
  • Oncogene Protein pp60(v-src) / metabolism*
  • RNA, Messenger / metabolism*
  • STAT3 Transcription Factor
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • ras Proteins / genetics
  • ras Proteins / metabolism*

Substances

  • DNA-Binding Proteins
  • RNA, Messenger
  • STAT3 Transcription Factor
  • Stat3 protein, mouse
  • Trans-Activators
  • Oncogene Protein pp60(v-src)
  • ras Proteins