GENE EXPRESSION IN LIVER CARCINOGENESIS

可能与肿瘤相关的特定基因的表达 大鼠肝脏在化学致癌过程中的转化 学习。这些基因将通过两种方式进行鉴定：1)已知的癌基因 将利用杂交技术检测它们在大鼠肝脏肿瘤中的表达 (32-P)标记的探针(RNA斑点杂交)。因为增加了 癌基因的表达水平经常与肿瘤相关 在其他癌症中，很有可能 癌基因转录本将在大鼠肝脏肿瘤中升高；2)其他肿瘤 特定的转录本将通过构建cDNA文库进行鉴定 从大鼠肝脏肿瘤的mRNA中提取，然后检测个体的杂交 从肿瘤和正常肝脏克隆~(32)P标记的mRNA。使用 这两种途径，在肝脏中含量升高的mRNA序列 与正常肝脏相比，癌症将被识别出来。如果之前 未知的信使核糖核酸被发现，它们所编码的蛋白质将被鉴定 通过计算机分析它们的cdna序列。 肿瘤特异性克隆将被用于研究两个重要问题 与正常肝脏相比，癌症将被识别出来。如果之前 未知的信使核糖核酸被发现，它们所编码的蛋白质将被鉴定 通过计算机分析它们的cdna序列。 肿瘤特异性克隆将被用于研究两个重要问题 致癌：1)组织切片和细胞的原位杂交 分离将被用来找出哪些细胞类型正在转录肿瘤 致癌过程中的特定基因，希望识别癌前病变 最终导致肿瘤的细胞群；2)肿瘤的模式 不同诱导肿瘤过程中肿瘤特异性基因的表达 将对致癌物质进行研究。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采取行动。

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.