Inactivation of the type II TGF-beta receptor in colon cancer cells with microsatellite instability.
Transforming growth factor-beta (TGF-beta) is a potent inhibitor of epithelial cell growth. Human colon cancer cell lines with high rates of microsatellite instability were found to harbor mutations in the type II TGF-beta receptor (RII) gene. Eight such examples, due to three different mutations, were identified. The mutations were clustered within small repeated sequences in the RII gene, were accompanied by the absence of cell surface RII receptors, and were usually associated with small amounts of RII transcript. RII mutation, by inducing the escape of cells from TGF-beta-mediated growth control, links DNA repair defects with a specific pathway of tumor progression.
Markowitz
S
S
Department of Medicine, University Hospitals of Cleveland, OH, USA.
Wang
J
J
Myeroff
L
L
Parsons
R
R
Sun
L
L
Lutterbaugh
J
J
Fan
R S
RS
Zborowska
E
E
Kinzler
K W
KW
Vogelstein
B
B
D000595:Amino Acid Sequence; D000818:Animals; D003110:Colonic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004260:DNA Repair; D004273:DNA, Neoplasm / Q000235:genetics; D004276:DNA, Satellite / Q000235:genetics*; D018450:Disease Progression; D016368:Frameshift Mutation; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009368:Neoplasm Transplantation; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics* / Q000378:metabolism; D012091:Repetitive Sequences, Nucleic Acid; D017384:Sequence Deletion; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D004276:DNA, Satellite; D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta