IL-2- and STAT5-regulated cytokine gene expression in cells expressing the Tax protein of HTLV-1

• Published in: Oncogene Vol. 24; no. 29; pp. 4624 - 4633
• Main Authors: FUNG, Michelle M, CHU, Yen-Lin, FINK, J. Lynn, WALLACE, Anne, MCGUIRE, Kathleen L
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing 07-07-2005; Nature Publishing Group
• Subjects: Bioinformatics; Biological and medical sciences; Cell Culture Techniques; Cell cycle; Cell growth; Cell physiology; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Cytokines; Cytokines - biosynthesis; DNA microarrays; DNA-Binding Proteins - metabolism; Fundamental and applied biological sciences. Psychology; Gene expression; Gene Expression Regulation, Neoplastic; Gene Products, tax - biosynthesis; Genotype & phenotype; Growth factors; Human T-lymphotropic virus 1 - physiology; Humans; Interleukin 13; Interleukin 2; Interleukin 5; Interleukin 9; Interleukin-2 - metabolism; Kinases; Leukemia; Lymphocytes; Lymphocytes T; Milk Proteins - metabolism; Molecular and cellular biology; Oligonucleotide Array Sequence Analysis; Phenotype; Phenotypes; Proteins; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction; Stat5 protein; STAT5 Transcription Factor; Tax protein; Thymus Gland - cytology; Trans-Activators - metabolism; Transformed cells; La Jolla California; United States > US; Human; Interleukin 2; T cell; Cytokine; HTLV-1; IL-2; Tax; Gene expression; Carcinogenesis; Protein
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/sj.onc.1208507

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.