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 (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.
Kim
S J
SJ
Laboratory of Chemoprevention, National Cancer Institute, Bethesda, Maryland 20892.
Kehrl
J H
JH
Burton
J
J
Tendler
C L
CL
Jeang
K T
KT
Danielpour
D
D
Thevenin
C
C
Kim
K Y
KY
Sporn
M B
MB
Roberts
A B
AB
D002460:Cell Line; D002872:Chromosome Deletion; D015870:Gene Expression; D015368:Human T-lymphotropic virus 1 / Q000235:genetics*; D006801:Humans; D015458:Leukemia, T-Cell / Q000235:genetics / Q000378:metabolism* / Q000382:microbiology; D009154:Mutation; D010957:Plasmids; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D015183:Restriction Mapping; D015534:Trans-Activators / Q000378:metabolism*; D014162:Transfection; D015291:Transforming Growth Factors / Q000096:biosynthesis / Q000235:genetics*
D012333:RNA, Messenger; D015534:Trans-Activators; D015291:Transforming Growth Factors