CXCR7 is inducible by HTLV-1 Tax and promotes growth and survival of HTLV-1-infected T cells.

Full 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.

Author information

Author/s: Jin, Zhe (Z); Nagakubo, Daisuke (D); Shirakawa, Aiko-Konno (AK); Nakayama, Takashi (T); Shigeta, Akiko (A); Hieshima, Kunio (K); Yamada, Yasuaki (Y); Yoshie, Osamu (O);

Affiliation: Department of Microbiology, Kinki University School of Medicine, Osaka-Sayama, Osaka, Japan.

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: International journal of cancer. Journal international du cancer (Int J Cancer), published in United States. (Language: eng)

Reference: 2009-Nov; vol 125 (issue 9) : pp 2229-35

Dates: Created 2009/09/03; Completed 2009/09/15;

PMID: 19623653, status: MEDLINE (last retrieval date: 9/15/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

External Links for this article
(including full text providers, if available):

Click Electronic Full-text Provider Links to see options for finding the electronic full text links to this article. Note there may be a subscription or fee required for access to the full text. See our FAQ for information on finding FREE full text articles.

This article may also be located in paper journal collections available in many libraries. Use the Journal and Publication Information above to find the full article.

MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Humans
NF-kappa B - metabolism
RNA, Messenger - analysis
Receptors, CXCR - genetics
T-Lymphocytes - physiology; virology

Associated Chemicals: CXCR7 protein, human (0) ; Gene Products, tax (0) ; NF-kappa B (0) ; RNA, Messenger (0) ; Receptors, CXCR (0) ; tax protein, Human T-lymphotrophic virus 1 (0)

These are the highest related articles currently in the database: