The molecular basis of retinoblastomas.
Retinoblastomas and osteosarcomas in humans are associated with the homozygous inactivation of the Rb gene which maps to a locus on chromosome 13q14. This gene has been isolated as molecular clones. The gene encodes a protein of 105 kDa which is a nuclear DNA-binding phosphoprotein. The protein is not found in 15 retinoblastomas studied so far. An independent line of work examining the transforming mechanisms of the adenovirus E1A oncogene has shown that its encoded oncoprotein complexes with the Rb-encoded p105 in virus-transformed cells. This suggests that the Rb protein acts at a central intersection in the cell's growth regulatory network. Its alteration by genetic or epigenetic mechanisms appears to represent a critical event in several different pathways of tumorigenesis.
Weinberg
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Department of Biology, Massachusetts Institute of Technology, Whitehead Institute of Biomedical Research, Cambridge 02142.
D002874:Chromosome Mapping; D003001:Cloning, Molecular; D005814:Genes, Viral; D006801:Humans; D009857:Oncogenes; D012516:Osteosarcoma / Q000235:genetics*; D012175:Retinoblastoma / Q000235:genetics*; D014407:Tumor Cells, Cultured / Q000503:physiopathology