1. CXCR7 is inducible by HTLV-1 Tax and promotes growth and survival of HTLV-1-infected T cells.
- Author
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Jin Z, Nagakubo D, Shirakawa AK, Nakayama T, Shigeta A, Hieshima K, Yamada Y, and Yoshie O
- Subjects
- Cell Line, Cell Proliferation, Cell Survival, Humans, NF-kappa B metabolism, RNA, Messenger analysis, Gene Products, tax physiology, Receptors, CXCR genetics, T-Lymphocytes physiology, T-Lymphocytes virology
- Abstract
Human T-lymphotropic virus type 1 (HTLV-1), the etiological agent of adult T-cell leukemia (ATL), encodes the potent transcriptional activator Tax, which is required for HTLV-1-induced immortalization of T cells. CXCR7 is an atypical chemokine receptor frequently expressed by tumor cells and known to promote cell growth and survival. We found that HTLV-1-immortalized T cells expressing Tax consistently expressed CXCR7. Induction of Tax in JPX-9 upregulated CXCR7. Wild-type Tax efficiently activated the CXCR7 promoter via a proximal NF-kappaB site, while a mutant Tax selectively defective in NF-kappaB activation did not. CCX754, a synthetic CXCR7 antagonist, inhibited cell growth and increased apoptosis of HTLV-1-immortalized T cells. Knockdown of CXCR7 by small interfering RNA also reduced cell growth. Stable expression of CXCR7 in a CXCR7-negative ATL cell line promoted cell growth and survival. Taken together, CXCR7 is inducible by Tax and may play an important role in HTLV-1-induced immortalization of T cells by promoting growth and survival of HTLV-1-infected T cells., ((c) 2009 UICC.)
- Published
- 2009
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