Frequent inactivation of the retinoblastoma anti-oncogene is restricted to a subset of human tumor cells.
We have used polyclonal anti-synthetic peptide serum to study the role of retinoblastoma gene (RB) inactivation in a variety of human tumor cell lines. Our analysis indicates that inactivation of the RB protein, p105-Rb, is universal in retinoblastoma cells, vindicating the predictions of the Knudson "two-hit" hypothesis. In addition, our analysis has shown that inactivations of the RB gene are nearly as frequent in a more common human tumor, small cell lung carcinoma. One-third of bladder carcinomas surveyed also carry altered or absent p105-Rb. Other human tumors by contrast demonstrate only infrequent inactivation of the RB gene. These results suggest that inactivation of the RB gene is a critical step in the pathogenesis of a subset of human tumors.
Horowitz
J M
JM
Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge 02142.
Park
S H
SH
Bogenmann
E
E
Cheng
J C
JC
Yandell
D W
DW
Kaye
F J
FJ
Minna
J D
JD
Dryja
T P
TP
Weinberg
R A
RA
D001483:Base Sequence; D015139:Blotting, Southern; D004273:DNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D005134:Eye Neoplasms / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008715:Methionine / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D009857:Oncogenes; D010750:Phosphoproteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics; D012175:Retinoblastoma / Q000235:genetics*; D016160:Retinoblastoma Protein; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured / Q000378:metabolism
D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; D016160:Retinoblastoma Protein; D008715:Methionine