Effects of IFN-gamma and Stat1 on gene expression, growth, and survival in non-small cell lung cancer cells.
Stat transcription factors are activated by cytokines and can activate pathways important in oncogenesis. Although previous studies have identified an oncogenic role of Stat3 in lung cancer cells, the role of Stat1 is unclear. Using a mutant of Stat1 with constitutive activity (Stat1C), we examined the effect of persistent Stat1 activity on lung cancer cell growth, survival and gene expression. We identified no significant effect of Stat1C alone or with interferon-gamma (IFN-gamma) on lung cancer cell growth or survival. Consistent with prior reports, Stat1C expression alone elicited minimal changes in gene expression and required costimulatory IFN-gamma for full activity. Using oligonucleotide gene arrays and quantitative real-time PCR, we identified numerous proinflammatory gene products and chemokines regulated by IFN-gamma/Stat1C signaling. These results suggest the major role of IFN-gamma and Stat1 in lung cells is to direct a proinflammatory gene expression program rather than have major effects on cell growth or survival or both.
Li
Jiannong
J
Thoracic Oncology/Experimental Therapeutics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA.
Yu
Bin
B
Song
Lanxi
L
Eschrich
Steve
S
Haura
Eric B
EB
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D018925:Chemokines / Q000096:biosynthesis / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology*; D050794:STAT1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics
D000998:Antiviral Agents; D018925:Chemokines; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D007371:Interferon-gamma