GENE EXPRESSION IN LIVER CARCINOGENESIS

可能参与肿瘤形成的特定基因的表达 在化学致癌过程中大鼠肝脏的转化将是 研究了 这些基因将通过两种方式进行鉴定：1）已知的癌基因 将使用杂交测试它们在大鼠肝肿瘤中的表达 用32-P标记的探针（RNA斑点印迹法）检测肝脏mRNA。 因为增加的 癌基因的表达水平通常与肿瘤的发生有关。 在其他癌症中，有一个很好的可能性， 在大鼠肝肿瘤中癌基因转录物将升高; 2）其他肿瘤 通过构建cDNA文库， 从大鼠肝肿瘤mRNA，然后测试杂交的个人 cDNA克隆与~（32）P标记的肿瘤和正常肝mRNA的杂交。 与 这两种方法，mRNA序列的数量在肝脏中升高， 将鉴别与正常肝脏相比的癌。 如果先前 发现未知的mRNA，它们编码的蛋白质将被鉴定 通过计算机分析它们的cDNA序列。 肿瘤特异性cDNA克隆将用于研究两个重要问题 将鉴别与正常肝脏相比的癌。 如果先前 发现未知的mRNA，它们编码的蛋白质将被鉴定 通过计算机分析它们的cDNA序列。 肿瘤特异性cDNA克隆将用于研究两个重要问题， 致癌作用：1）组织切片和细胞的原位杂交 将使用分级来发现哪些细胞类型正在转录肿瘤 癌发生过程中的特定基因，希望能识别癌前病变， 最终导致肿瘤的细胞群; 2） 在用不同的药物诱导肿瘤期间肿瘤特异性基因的表达 致癌物质将被研究。 不同致癌物之间的比较可能 确定它们是通过共同的机制还是通过不同的机制起作用。

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.