GROWTH-INHIBITION BY TRANSFORMING GROWTH FACTOR-BETA(TGF-BETA) TYPE-IIS RESTORED IN TGF-BETA-RESISTANT HEPATOMA-CELLS AFTER EXPRESSION OF TGF-BETA RECEPTOR TYPE-II CDNA
M. Inagaki et al., GROWTH-INHIBITION BY TRANSFORMING GROWTH FACTOR-BETA(TGF-BETA) TYPE-IIS RESTORED IN TGF-BETA-RESISTANT HEPATOMA-CELLS AFTER EXPRESSION OF TGF-BETA RECEPTOR TYPE-II CDNA, Proceedings of the National Academy of Sciences of the United Statesof America, 90(11), 1993, pp. 5359-5363
The growth of human hepatoma Hep 3B cells is potently inhibited by TGF
-beta1 (ID50 = 0.2 ng/ml, 8 pM). A mutant cell line was derived that w
as not inhibited in growth by TGF-beta1 at 5 ng/ml (200 pM) and that l
acked TGF-beta receptor type II (TGF-betaRII) gene. Transfection of th
e cloned cDNA for human TGF-betaRII to this mutant cell line restored
receptor expression as well as the inhibition in growth by TGF-beta1.
In both wild-type and mutant cells stably transfected with TGF-betaRII
cDNA, TGF-betaRII coimmunoprecipitated with TGF-beta receptor type I
in the presence of ligand. These experiments provide direct evidence f
or the role of TGF-betaRII in the inhibitory effect of TGF-beta on gro
wth and suggest that TGF-betaRII acts by means of a heteromeric surfac
e complex with TGF-beta receptor type I.