IL-2- and STAT5-regulated cytokine gene expression in cells expressing the Tax protein of HTLV-1.
Interleukin-2 (IL-2) mediates cell cycle progression and antiapoptosis in human T cells via several signal transduction pathways. The Tax protein of the human T-cell leukemia virus type I (HTLV-1) deregulates cell growth and alters the role of IL-2 in infected cells. However, Tax-immortalized cells stay dependent on IL-2, suggesting that events besides HTLV-1 gene expression are required for leukemia to develop. Here, IL-2-dependent and -independent events were analysed in a human T cell line immortalized by Tax. These studies show that, of the signaling pathways evaluated, only STAT5 remains dependent. Microarray analyses revealed several genes, including il-5, il-9 and il-13, are uniquely upregulated by IL-2 in the presence of Tax. Bioinformatics and supporting molecular biology show that some of these genes are STAT5 targets, explaining their IL-2 upregulation. These results suggest that IL-2 and viral proteins work together to induce gene expression, promoting the hypothesis that deregulation via the constitutive activation of STAT5 may lead to the IL-2-independent phenotype of HTLV-1-transformed cells.
Fung
Michelle M
MM
Department of Biology, San Diego State University, 5500 Campanile Drive, San Diego, CA 92182-4614, USA.
Chu
Yen-Lin
YL
Fink
J Lynn
JL
Wallace
Anne
A
McGuire
Kathleen L
KL
D018929:Cell Culture Techniques; D016207:Cytokines / Q000096:biosynthesis*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D016356:Gene Products, tax / Q000096:biosynthesis*; D015368:Human T-lymphotropic virus 1 / Q000502:physiology*; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism*; D008894:Milk Proteins / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050799:STAT5 Transcription Factor; D015398:Signal Transduction; D013950:Thymus Gland / Q000166:cytology; D015534:Trans-Activators / Q000378:metabolism*
D016207:Cytokines; D004268:DNA-Binding Proteins; D016356:Gene Products, tax; D007376:Interleukin-2; D008894:Milk Proteins; D050799:STAT5 Transcription Factor; D015534:Trans-Activators