DETECTION OF ALTERED APC PROTEINS IN COLON CANCER CELLS

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Mutations in the APC gene appear to be crucial for adenoma formation in inherited Familial Adenomatous Polyposis (FAP) and in the early stages of colorectal cancer. Analysis of the APC gene has identified mutations in germ line DNA of FAP patients. Over 90% of the mutations interrupt the reading frame suggesting the presence of a truncated APC protein. We have developed a series of anti-APC antibodies directed against the amino terminal portion of APC. These antibodies have identified a truncated form of APC protein in SW480 cells carrying mutated APC alleles. We will examine a series of tumor cell lines and normal cells for altered forms of APC protein associated with the presence of colorectal cancer. We will concentrate on cell lines in which the structure of APC is known, either wild type of mutated. We will also begin generating antibodies to carboxyl terminal domains in APC that will be used to discriminate full length versus truncated APC proteins. In Phase II, the combination of anti-amino terminal and anti-carboxyl terminal APC antibodies will be used to develop an assay for determination of APC status in clinical samples as a prognostic test for FAP and colorectal cancer.