GENE EXPRESSION IN LIVER CARCINOGENESIS

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The expression of specific genes which may be involved in the neoplastic transformation of rat liver during chemical carcinogenesis will be studied. These genes will be identified in two ways: 1) known oncogenes will be tested for their expression in rat liver tumors using hybridization of liver mRNA to (32-P) labelled probes (RNA dot-blots). Because increased levels of oncogene expression are frequently correlated with the neoplastic state in other cancers, there is a good possibility that the levels of oncogene transcripts will be elevated in rat liver tumors; 2) other tumor specific transcripts will be identified by constructing a cDNA library made from rat liver tumor mRNA, and then testing the hybridization of individual cDNA clones to (32-P) labelled mRNA from tumor and from normal liver. With these two approaches, mRNA sequences whose amounts are elevated in liver carcinomas compared to normal liver will be identified. If previously unknown mRNA's are found, the proteins which they encode will be identified by a computer analysis of their cDNA sequences. Tumor specific cDNA clones will be used to study two important problems in carcinomas compared to normal liver will be identified. If previously unknown mRNA's are found, the proteins which they encode will be identified by a computer analysis of their cDNA sequences. Tumor specific cDNA clones will be used to study two important problems in carcinogenesis: 1) in situ hybridization of tissue sections and cell fractionation will be used to find which cell types are transcribing tumor specific genes during carcinogenesis, in hopes of identifying premalignant cell populations which ultimately give rise to tumors; 2) the pattern of expression of tumor specific genes during tumnor induction with different carcinogens will be studied. Comparisons among different carcinogens may determine whether they act by common or by distinct mechanisms.