Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving antigen-antibody binding – specific binding protein...
Patent
1994-05-18
1996-08-27
Fleisher, Mindy
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving antigen-antibody binding, specific binding protein...
435 72, 435 721, 435 723, G01N 3353, G01N 33566
Patent
active
055500234
ABSTRACT:
A human gene has been discovered which is genetically altered in human tumor cells. The genetic alteration is gene amplification and leads to a corresponding increase in gene products. Detecting that the gene, designated hMDM2, has become amplified or detecting increased expression of gene products is diagnostic of tumorigenesis. Human MDM2 protein binds to human p53 and allows the cell to escape from p53-regulated growth. Methods of identifying compounds which interfere with the binding of human MDM2 protein to human p53 protein involve measuring the amounts of the proteins bound, displaced, or prevented from binding, in the presence of test compounds.
REFERENCES:
Fakharzadeh, et al., "Tumorigenic Potential Associated with Enhanced Expression of a Gene That is Amplified in a Mouse Tumor Cell Line", The EMBO Journal, 10(6):1565-1569 (1991).
Hinds, et al., "Mutant p53 DNA Clones From Human Colon Carcinomas Cooperate With Ras in Transforming Primary Rat Cells: A Comparison of the Hot Spot Mutant Phenotypes," Cell Growth & Differential, 1:561-580 (1990).
Romkes, et al., "Cloning and Expression of cDNA for Multiple Members of the Human Cytochrome P450IIC Subfamily", Biochemistry, 30(13):3247-3255 (1991).
Momand, et al., "The MDM2 Oncogene Product Forms a Complex with the p53 Protein and Inhibits p53-Mediated Transactivation," Cell:69:1237-1245 (1992).
Oliner, et al., "Amplification of a Gene Encoding a p53-Associated Protein in Human Sarcomas", Nature, 358:80-83 (1992).
Ladanyi, et al., "MDM2 Gene Amplification in Metastatic Osteosarcoma", Cancer Research, 53:16-18 (1993).
Leach, et al., "p53 Mutation and MDMS Amplification in Human Soft Tissue Sarcomas", Cancer Research 53:2231-2234 (1993).
Oliner, et al., "Oncoprotein MDM2 Conceals the Activation Domain of Tumour Suppressor p53", Nature, 362(6423):857-860 (1993).
Cahilly-Snyder, "Molecular Analysis and Chromosomal Mapping of Amplified Genes Isolated From a Transformed Mouse 3T3 Cell Line", Somatic Cell and Molecular Genetics, 13(3):235-244 (1987).
Kinzler Kenneth W.
Vogelstein Bert
Fleisher Mindy
Guzo David
The Johns Hopkins University
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