[CCR4, HTLV-1 infection, and ATL oncogenesis].
Adult T-cell leukemia (ATL) is a malignancy of mature CD4+ T cells that is etiologically associated with the infection of human T-cell leukemia virus type 1 (HTLV-1), an exogenous human retrovirus. Previously, we have shown that leukemic cells of most ATL patients express CCR4, a chemokine receptor known to be selectively expressed by T cell subsets such as Th2 cells, skin-homing memory/effector T cells, and regulatory T cells. Therefore, the expression of CCR4 suggests that ATL cells are mostly derived from one of these T cell subsets. We have also shown that Tax, the HTLV-1-encoded potent transcriptional activator, strongly induces the expression of CCL22, a CCR4 ligand, which promotes the cell-dependent transmission of HTLV-1 from HTLV-1-infected T cells to CCR4+ target T cells by inducing close cell-to-cell interactions. We have also shown that ATL cells aberrantly express the AP-1 family member Fra-2 which, by forming the heterodimer with JunD, potently induces the expression of not only CCR4 but also the genes such as c-Myb, MDM2 and Bcl-6, the well-known proto-oncogenes. Thus, Fra-2 is a novel oncogene of ATL, and CCR4 may be regarded as a useful tumor marker of ATL.
Yoshie
Osamu
O
Department of Microbiology, Kinki University School of Medicine, Osaka 589-8511, Japan. o.yoshie@med.kindai.ac.jp
D014408:Biomarkers, Tumor; D051921:Fos-Related Antigen-2 / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic; D015368:Human T-lymphotropic virus 1 / Q000472:pathogenicity; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000821:virology*; D016755:Proto-Oncogene Proteins c-jun / Q000502:physiology; D011519:Proto-Oncogenes / Q000235:genetics; D054398:Receptors, CCR4; D016176:T-Lymphocyte Subsets / Q000821:virology*
D014408:Biomarkers, Tumor; D051921:Fos-Related Antigen-2; D016755:Proto-Oncogene Proteins c-jun; D054398:Receptors, CCR4