(TGF-01) Gene by Human T Lymphotropic Virus Type 1 Tax: A Potential Mechanism for the Increased Production of TGF-01 in AdultT Cell Leukemia

Summary We examined the effect of the humanT lymphotropic virus type 1 (HTLVI) Tax gene product on thehuman 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-infectedT cell lines . We report that fresh leukemic cells from ATL patients constitutively produce high levels ofTGF-01 mRNA and secreteTGF-a1 but not TGF-/32 into the culturemedium. In addition, long-term ATL cell lines expressed significant amounts of TGF-/31 mRNA as well as detectable levels ofTGF-01 protein . These results suggest a role for Tax in the upregulation of TGF-a1 in HTLVI-infected cells.

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