Our recent experiments have demonstrated that the p53 gene is a suppressor of human tumor growth and that this gene is mutated in a large number of human cancers. These cancers include those of the brain, colon, lung, breast, ovary, bone and bladder; indeed, p53 is the most commonly mutated gene yet identified in human tumors, genetically altered in nearly half the total cancers that occur in the United States annually. Understanding the role of the p53 gene in human tumorigenesis therefore has become a critically important research goal. This proposal is designed to continue our investigations on p53 through a variety of approaches, including (i) clinical studies, to define the timing of p53 gene mutations during the course of human tumorigenesis, and the prevalence of inherited gene mutations in families predisposed to cancer development; (ii) physiologic studies, to examine the effects of wild-type and mutant p53 expression on the growth and cell cycle control of cancer cells containing endogenous p53 gene mutations; (iii) genetic studies, to discover genes that modulate p53 action in vivo, in both mammalian and lower eukaryotic environments; and (iv) biochemical studies, to identify DNA sequences and cellular proteins to which p53 binds in vitro and in vivo. Each of these approaches has the potential to illuminate specific aspects of p53 function. In combination, they should lead to new insights into the biology of a prototype tumor suppressor gene, with implications for diverse forms of human neoplasia.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA043460-12
Application #
2091181
Study Section
Pathology B Study Section (PTHB)
Project Start
1983-08-01
Project End
1996-05-31
Budget Start
1994-06-01
Budget End
1995-05-31
Support Year
12
Fiscal Year
1994
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218
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