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

J Exp Med. 1990 Jul 1;172(1):121-9. doi: 10.1084/jem.172.1.121.

Abstract

We examined the effect of the human T lymphotropic virus type 1 (HTLV-I) Tax gene product on the human transforming growth factor beta 1 (TGF-beta 1) promoter. Transfection of deleted constructs of the TGF-beta 1 promoter revealed regions homologous with AP-1 binding sites that were required for Tax-induced transactivation of the TGF-beta 1 promoter. In addition, we examined the expression and secretion of TGF-beta in fresh leukemic cells isolated from patients with adult T cell leukemia (ATL) and in HTLV-1-infected T cell lines. We report that fresh leukemic cells from ATL patients constitutively produce high levels of TGF-beta 1 mRNA and secrete TGF-beta 1 but not TGF-beta 2 into the culture medium. In addition, long-term ATL cell lines expressed significant amounts of TGF-beta 1 mRNA as well as detectable levels of TGF-beta 1 protein. These results suggest a role for Tax in the upregulation of TGF-beta 1 in HTLV-I-infected cells.

MeSH terms

  • Cell Line
  • Chromosome Deletion
  • Gene Expression*
  • Human T-lymphotropic virus 1 / genetics*
  • Humans
  • Leukemia, T-Cell / genetics
  • Leukemia, T-Cell / metabolism*
  • Leukemia, T-Cell / microbiology
  • Mutation
  • Plasmids
  • Promoter Regions, Genetic
  • RNA, Messenger / genetics
  • Restriction Mapping
  • Trans-Activators / metabolism*
  • Transfection
  • Transforming Growth Factors / biosynthesis
  • Transforming Growth Factors / genetics*

Substances

  • RNA, Messenger
  • Trans-Activators
  • Transforming Growth Factors