Transactivation of the Transforming Growth Factor 01 ( TGF - 01 ) Gene by Human T Lymphotropic Virus Type 1 Tax : A Potential Mechanism for the Increased Production of TGF - 01 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-01) promoter. Transfection ofdeleted constructs ofthe TGF-fl1 promoter revealed regions homologous with AP-1 binding sites that were required for Tax-induced transactivation of the TGF-(31 promoter. In addition, we examined the expression and secretion ofTGF-,3 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-/32 into the culture medium. In addition, long-term ATL cell lines expressed significant amounts of TGF-/31 mRNA as well as detectable levels of TGF-01 protein . These results suggest a role for Tax in the upregulation of TGF-a1 in HTLVI-infected cells.