GROWTH-INHIBITION BY TRANSFORMING GROWTH FACTOR-BETA(TGF-BETA) TYPE-I IS RESTORED IN TGF-BETA-RESISTANT HEPATOMA-CELLS AFTER EXPRESSION OF TGF-BETA RECEPTOR TYPE-II CDNA

被引:209
作者
INAGAKI, M
MOUSTAKAS, A
LIN, HY
LODISH, HF
CARR, BI
机构
[1] UNIV PITTSBURGH,PITTSBURGH TRANSPLANTAT INST,PITTSBURGH,PA 15260
[2] WHITEHEAD INST BIOMED RES,CAMBRIDGE,MA 02142
[3] MIT,DEPT BIOL,CAMBRIDGE,MA 02139
关键词
HUMAN HEPATOMA; TRANSFECTION; POLYCLONAL ANTISERA;
D O I
10.1073/pnas.90.11.5359
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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 was not inhibited in growth by TGF-beta1 at 5 ng/ml (200 pM) and that lacked TGF-beta receptor type II (TGF-betaRII) gene. Transfection of the 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 for the role of TGF-betaRII in the inhibitory effect of TGF-beta on growth and suggest that TGF-betaRII acts by means of a heteromeric surface complex with TGF-beta receptor type I.
引用
收藏
页码:5359 / 5363
页数:5
相关论文
共 33 条
[1]  
BOYD FT, 1989, J BIOL CHEM, V264, P2272
[2]  
CARR BI, 1986, CANCER RES, V44, P2230
[3]   THE TRANSFORMING GROWTH-FACTOR-BETA SYSTEM, A COMPLEX PATTERN OF CROSS-REACTIVE LIGANDS AND RECEPTORS [J].
CHEIFETZ, S ;
WEATHERBEE, JA ;
TSANG, MLS ;
ANDERSON, JK ;
MOLE, JE ;
LUCAS, R ;
MASSAGUE, J .
CELL, 1987, 48 (03) :409-415
[4]  
CHEIFETZ S, 1988, J BIOL CHEM, V263, P16984
[5]  
CHEIFETZ S, 1986, J BIOL CHEM, V261, P9972
[6]   STRUCTURE AND PROPERTIES OF THE CELLULAR RECEPTOR FOR TRANSFORMING GROWTH-FACTOR TYPE-BETA [J].
FANGER, BO ;
WAKEFIELD, LM ;
SPORN, MB .
BIOCHEMISTRY, 1986, 25 (11) :3083-3091
[7]   TGF-BETA IN LIVER DEVELOPMENT, REGENERATION, AND CARCINOGENESIS [J].
FAUSTO, N ;
MEAD, JE ;
GRUPPUSO, PA ;
BRAUN, L .
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES, 1990, 593 :231-242
[8]  
FROLIK CA, 1984, J BIOL CHEM, V259, P995
[9]  
GEISER AG, 1992, J BIOL CHEM, V267, P2588
[10]   A HUMAN BETA-ACTIN EXPRESSION VECTOR SYSTEM DIRECTS HIGH-LEVEL ACCUMULATION OF ANTISENSE TRANSCRIPTS [J].
GUNNING, P ;
LEAVITT, J ;
MUSCAT, G ;
NG, SY ;
KEDES, L .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1987, 84 (14) :4831-4835