Transcriptional profile of Rous Sarcoma Virus transformed chicken embryo fibroblasts reveals new signaling targets of viral- src

• Published in: Virology (New York, N.Y.) Vol. 364; no. 1; pp. 10 - 20
• Main Authors: Masker, Kathryn, Golden, Alicia, Gaffney, Christian J, Mazack, Virginia, Schwindinger, William F, Zhang, Weizhou, Wang, Lu-Hai, Carey, David J, Sudol, Marius
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 20.07.2007
• Subjects: Animals; Avian sarcoma; Base Sequence; Cell Transformation, Viral - genetics; Cells, Cultured; Chick Embryo; chickens; cultured cells; DNA Primers - genetics; DNA, Viral - genetics; embryo (animal); fibroblasts; Follistatin; Gene Expression Profiling; gene expression regulation; Genes, src; Genes, Viral; genetic transformation; Infectious Disease; MAP kinase phosphatase 2; Models, Genetic; Oligonucleotide Array Sequence Analysis; oncogene protein v-src; oncogenes; Protein-tyrosine kinase; protein-tyrosine kinases; reverse transcriptase polymerase chain reaction; Rous sarcoma virus; Rous sarcoma virus - genetics; Rous sarcoma virus - pathogenicity; Rous sarcoma virus - physiology; Schmidt-Ruppin strain of RSV; Signal Transduction; src oncogene; transcription (genetics); Transcription, Genetic; Vasoactive intestinal polypeptide; viral proteins; Follistatin; Schmidt-Ruppin strain of RSV; Vasoactive intestinal polypeptide; Avian sarcoma; src oncogene; Protein-tyrosine kinase; MAP kinase phosphatase 2
• ISSN: 0042-6822; 1096-0341
• DOI: 10.1016/j.virol.2007.03.026

Abstract Transformation of chicken fibroblasts in vitro by Rous Sarcoma Virus represents a model of cancer in which a single oncogene, viral src , uniformly and rapidly transforms primary cells in culture. We experimentally surveyed the transcriptional program affected by Rous Sarcoma Virus (RSV) in primary culture of chicken embryo fibroblasts. As a control, we used cells infected with non-transforming RSV mutant td106, in which the src gene was deleted. Using Affymetrix GeneChip® Chicken Genome Arrays, we report 811 genes that were modulated more than 2.5 fold in the virus transformed cells. Among these, 409 genes were induced and 402 genes were repressed by viral src . From the repertoire of modulated genes, we selected 20 genes that were robustly changed. We then validated and quantified the transcriptional changes of most of the 20 selected genes by real-time PCR. The set of strongly induced genes contains vasoactive intestinal polypeptide, MAP kinase phosphatase 2 and follistatin, among others. The set of strongly repressed genes contains TGF beta 3, TGF beta-induced gene, and deiodinase. The function of several robustly modulated genes sheds new light on the molecular mechanism of oncogenic transformation.