课件16癌基因、抑

1、第 二 十 章 癌基因、抑癌基因与生长因子Oncogenes, Tumor suppressor gene and Growth Factors目 录癌基因、抑癌基因与生长因子的关系癌基因抑癌基因细胞生长因子正调控负调控产物第 一 节 癌 基 因Oncogenes癌基因(oncogene)细胞内控制细胞生长和分化的基因，它的结构异常或表达异常，可以引起细胞癌变。Definitions Oncogenes are the genes that are capable of transforming a normal cell into a cancerous cell, leading to a

2、 change of the hereditary character of their coding region or regulating area under certain condition. Oncogenes can be divided into two kinds:Oncogenes are also seen in oncogenic viruses. (Viraloncogenes are derived from normal host genes that have e incorporated into the viral genome and subsequen

3、tly undergo mutation.)Oncogenes result from the mutation of normal genes (proto-oncogenes or cellular oncogene).病毒癌基因(virus oncogene,v-onc)存在于病毒基因组中的癌基因，它不编码病毒的结构成分，对病毒复制也没有作用，但可以使细胞持续增殖。一、病毒癌基因 调节和启动转录 LTR gag pol env src LTR 长末端重复序列癌基因正常的病毒基因产生病毒核心蛋白产生逆转录酶和整合酶 产生病毒 外膜蛋白产生酪氨酸 激酶*病毒基因组结构目 录二、细胞癌基因细胞

4、癌基因(cellular-oncogene, c-onc)存在于生物正常细胞基因组中的癌基因，或称原癌基因 (proto-oncogenes , pro-onc) 。Proto-oncogenes OncogeneProto-oncogene: normal cell gene, involved in the control of normal cell growth and proliferation (cell cycle control, transcription factor, DNA repair gene)oncogene: mutated/de-regulated proto

5、-oncogene gene whose inappropriate expression leads to cancer细胞癌基因的特点广泛存在于生物界中；基因序列高度保守；作用通过其产物蛋白质来体现；被激活后，形成癌性的细胞转化基因。细胞癌基因的分类及其产物根据原癌基因的表达产物在细胞中的定位和功能分为：1. src家族 酪氨酸蛋白激酶2. ras家族 P213. myc家族 核内DNA结合蛋白4. sis家族 P28(类人血小板源生长因子)5. myb家族 核内转录因子目 录（一）获得启动子与增强子 proto-oncogene obtaining promotor and enhanc

6、er（二）基因易位 gene translocation（三）原癌基因扩增 Gene amplification（四）点突变 mutation出现新的表达产物 出现过量的正常表达产物出现异常、截短的表达产物三、癌基因活化的机制癌基因被激活的结果（一）细胞外生长因子 sis-P28（二）跨膜的生长因子受体c-src、c-abl、c-mos 、c-raf（三）细胞内信号传导体c-src、c-abl、c-ras、c-mas、H-ras、K-ras、N-ras、crk（四）核内转录因子 myc、fos四、原癌基因的产物与功能目 录 It may be helpful to think of a cel

7、l as a car. For it to work properly, there need to be ways to control how fast it goes. A proto-oncogene normally functions in a way that is similar to a gas pedal - it helps the cell grow and divide. An oncogene could be compared to a gas pedal that is stuck down, which causes the cell to divide ou

8、t of control. 第 二 节抑 癌 基 因Anti-oncogenes抑癌基因(cancer suppressive gene, anti-oncegene)抑制细胞过度生长、增殖从而遏制肿瘤形成的基因。一、抑癌基因的基本概念Tumor Suppressor Genes Tumor suppressor genes are cellular genes that normally suppress cell growth and proliferation. Tumor Suppressor Genes function to prevent malignant transforma

9、tion, Usually act in a recessive fashion. 细胞杂交试验正常细胞肿瘤细胞非肿瘤型杂交细胞杂交融合肿瘤细胞1肿瘤细胞2杂交融合非肿瘤型杂交细胞正常细胞失去某些基因肿瘤细胞二、常见的抑癌基因（一）视网膜母细胞瘤基因（Rb基因）G0 G1期Rb蛋白E-2FS期E-2FDNAmRNADNA三、抑癌基因的作用机制PRb蛋白（二）P53蛋白基因卫士P53蛋白解链酶复制因子AP21蛋白细胞停滞于G1期细胞自杀酸性区核心区碱性区P53蛋白 DNA损伤P21基因P53蛋白抑 制P53蛋白成功修复修复失败 A tumor suppressor gene is like th

10、e brake pedal on a car it normally keeps the cell from dividing too quickly just as a brake keeps a car from going too fast. When something goes wrong with the gene, such as a mutation, cell division can get out of control. An important difference between oncogenes and tumor suppressor genes is that

11、 oncogenes result from the activation (turning on) of proto-oncogenes, but tumor suppressor genes cause cancer when they are inactivated (turned off). 第 三 节生 长 因 子Growth factors 生长因子(growth factor) 通过质膜上特异的受体，将信息传递至细胞内部，调节细胞生长与增殖的多肽类物质。一、概述Growth factorsDefinition protein or peptide that secreted by

12、 cells play the function of signal transmitting between the cells and promote cell proliferation and differentiation, be called cell factor or cytokine also. 作用模式 内分泌 (endocrine)旁分泌 (paracrine)自分泌 (autocrine)Exert its function by three ways Endocrine Paracrine autocrine The same growth factor acts on different cells and bring different functions,the same cell can be affected by regulation of different growth factors. serum contains many kinds of growth factors.产生相应第二信使胞内相关蛋白质被磷酸化与膜受体结合酪氨酸激酶活化蛋白激酶活化 核内转录因子活化基因转录与胞内受体结合生长因子 受体复合物，活化相关基因二、生长因子作用机制目 录在某些生理