分子生物学原理(癌症)要点.ppt

v-Src protein is a constitutively active mutant form of c-Src protein, a protein-tyrosine kinase In cells containing an integrated RSV genome: a. v-src transcribed at inappropriately high rate level, b. The unregulated activity of v-Src protein causes continuos and inappropriate phosphorylation of target proteins. V-src is a dominant gain-of-function mutant of c-src, since v-src can induce cell transformation in the presence of the normal c-src proto-oncogene. Many other oncogenes derived from cellular proto-oncogenes have been found in different retroviruses, implying that the normal vertebrate genome contains many potential cancer-causing genes. The DNA transfection experiment has led to the molecular cloning of a ras gene with a single point mutation in human bladder tumors, a dominant gain-of-function oncogene. This oncogene , designated Ha-ras, also is present in Harvey sarcoma virus, a retrovirus. Similar experiments have led to the cloning of numerous oncogenes from tumor-cell DNA. Many of these cancer-causing genes are also found in various animal retroviruses. Slow-acting carcinogenic retroviruses can activate cellular proto-oncogenes Rous sarcoma virus induces tumors within days while most oncogenic retroviruses induce cancer only after a period of months or years. RSV carries the v-src oncogene in its genome while most oncogenic retroviruses lack an oncogene The site of integration in the cells from tumors caused by avian leukosis viruses is near the c-myc gene suggested that these slow-acting viruses cause disease by activating expression of c-Myc. These viruses act slowly both becausse integration near c-myc is a random, rare event and because additional mutants have to occur before a full-fledged tumor becomes evident. These mechanisms of oncogene activation--called promoter insertion and enhancer insertion--operate in a variety of oncogenes and have been implicated in many animal tumors caused by slow