The broad goals of this research program are to identify oncogene and oncogene products that play a role in the genesis of human colon cancer and to understand the basis for their action in normal and malignant cells. In particular these studies are directed towards determining if a correlation exists between changes in oncogene structure or expression and tumor progression and/or clinical course. This proposal addresses two issues: (1) the use of cell culture transformation systems to detect oncogenes active in premalignant and malignant colon tissue; and (2) an evaluation of a recently developed method for selecting cells that express oncogenes, the serum-free assay. DNAs isolated from carcinomas, polyps and matched normal colonic mucosa were introduced to NIH3T3 cells by transfection and scored either for their ability to induce foci on a monolayer of untransformed cells in serum-supplemented medium, or to induce the proliferation of cells in a defined culture medium from which a single essential growth factor was omitted. Two cell lines are currently being studies which: (a) proliferate in a serum-free medium from which the essential factor, platelet- derived growth factor (PDGF) has been omitted; (b) retain a flat morphology; (c) contain human sequences which segregate with the phenotype through multiple rounds of transfection and selection. One of these lines was derived from selections in which the original DNA was derived from an adenocarcinoma. The other line originated by transfection using DNA isolated from the lymphocytes of a patient with Gardner's syndrome, a condition that is predisposing to the development of colon cancer. These genes will be isolated by cloning. Their structure and expression in normal and malignant tissue will be examined. The serum-free media selection system will also be evaluated by screening additional DNA samples under various selective conditions.
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| Melhem, M F; Meisler, A I; Finley, G G et al. (1992) Distribution of cells expressing myc proteins in human colorectal epithelium, polyps, and malignant tumors. Cancer Res 52:5853-64 |
| Pogue-Geile, K; Geiser, J R; Shu, M et al. (1991) Ribosomal protein genes are overexpressed in colorectal cancer: isolation of a cDNA clone encoding the human S3 ribosomal protein. Mol Cell Biol 11:3842-9 |
| Finley, G G; Schulz, N T; Hill, S A et al. (1989) Expression of the myc gene family in different stages of human colorectal cancer. Oncogene 4:963-71 |
