Abstract
The growth of human hepatoma Hep 3B cells is potently inhibited by TGF-beta 1 (ID50 = 0.2 ng/ml, 8 pM). A mutant cell line was derived that was not inhibited in growth by TGF-beta 1 at 5 ng/ml (200 pM) and that lacked TGF-beta receptor type II (TGF-beta RII) gene. Transfection of the cloned cDNA for human TGF-beta RII to this mutant cell line restored receptor expression as well as the inhibition in growth by TGF-beta 1. In both wild-type and mutant cells stably transfected with TGF-beta RII cDNA, TGF-beta RII coimmunoprecipitated with TGF-beta receptor type I in the presence of ligand. These experiments provide direct evidence for the role of TGF-beta RII in the inhibitory effect of TGF-beta on growth and suggest that TGF-beta RII acts by means of a heteromeric surface complex with TGF-beta receptor type I.
Publication types
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Affinity Labels
-
Antibodies
-
Blotting, Southern
-
Carcinoma, Hepatocellular
-
Cell Division / drug effects*
-
Cell Membrane / metabolism
-
Drug Resistance / physiology*
-
Humans
-
Iodine Radioisotopes
-
Kinetics
-
Liver Neoplasms
-
Plasmids
-
RNA, Messenger / isolation & purification
-
RNA, Messenger / metabolism
-
Receptors, Cell Surface / genetics
-
Receptors, Cell Surface / isolation & purification
-
Receptors, Cell Surface / metabolism*
-
Receptors, Transforming Growth Factor beta
-
Recombinant Proteins / isolation & purification
-
Recombinant Proteins / metabolism
-
Transfection
-
Transforming Growth Factor beta / metabolism
-
Transforming Growth Factor beta / pharmacology*
-
Tumor Cells, Cultured
Substances
-
Affinity Labels
-
Antibodies
-
Iodine Radioisotopes
-
RNA, Messenger
-
Receptors, Cell Surface
-
Receptors, Transforming Growth Factor beta
-
Recombinant Proteins
-
Transforming Growth Factor beta