TRANSACTIVATION OF THE TRANSFORMING GROWTH FACTOR-BETA-1 (TGF-BETA-1) GENE BY HUMAN-T LYMPHOTROPIC VIRUS TYPE-1 TAX - A POTENTIAL MECHANISM FOR THE INCREASED PRODUCTION OF TGF-BETA-1 IN ADULT T-CELL LEUKEMIA

We examined the effect of the human T lymphotropic virus type 1 (HTLVI) Tax gene product on the human transforming growth factor 01(TGF-β1) promoter. Transfection ofdeleted constructs ofthe TGF-β1 promoter revealed regions homologous with AP-1 binding sites that were required for Tax-induced transactivation of the TGF-β1 promoter. In addition, we examined the expression and secretion of TGF-β1 in fresh leukemic cells isolated from patients with adult T cell leukemia (ATL) and in HTLV1-infected T cell lines. We report that fresh leukemic cells from ATL patients constitutively produce high levels of TGF-01 mRNA and secrete TGF-a1 but not TGF-β2 into the culture medium. In addition, long-term ATL cell lines expressed significant amounts of TGF-β1 mRNA as well as detectable levels of TGF-01 protein. These results suggest a role for Tax in the upregulation of TGF-β1 in HTLVI-infected cells. © 1990, Rockefeller University Press., All rights reserved.