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Transcriptional profile of Rous Sarcoma Virus transformed chicken embryo fibroblasts reveals new signaling targets of viral src
Author(s) -
Sudol Marius,
Masker Kathy,
Golden Alicia,
Gaffney Christian,
Zhang Weizhou,
Wang LuHai,
Carey David J
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a991
Transformation of chicken embryo fibroblasts (CEFs) in vitro by Rous Sarcoma Virus represents an important model of cancer, in which a single oncogene, viral src, uniformly and rapidly transforms primary cells in culture. We surveyed the transcriptional program affected by Rous Sarcoma Virus (RSV) in primary culture of CEFs. As a control, we used cells infected with non‐transforming RSV mutant td106 in which the src gene was deleted. Using GeneChip R Chicken Genome Arrays that cover 32,773 transcripts corresponding to 28,418 predicted genes, 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 at the level of transcription by viral src. From the repertoire of modulated genes, we selected 20 genes that were most robustly changed (from 190 to 5 fold). We then quantified the transcriptional changes of the 20 selected genes by real‐time PCR. The set of strongly induced genes contains vasoactive intestinal peptide, MAP kinase phosphatase 2 and follistatin, among others. The set of strongly repressed genes contains TGF beta 3, TGEF beta‐induced gene, and deiodinase. The function of several robustly induced and repressed genes sheds new light on the molecular mechanism of oncogenic transformation. Moreover, the human homologues of the viral‐src modulated chicken genes could represent biomarkers of those human cancers in which cellular src is activated.