chapter 14 癌基因与抑癌基因

nullnullLiyan XuOncogene Cancer suppressive genenullThe basic concept 1 oncogene: These genes code for proteins that are capable of stimulating cell growth and division. In normal tissues and organisms, such growth-stimulating proteins are regulated, so that growth is appropriately limited. However, changes/mutation in these genes may result in loss of growth regulation, leading to uncontrolled cell proliferation and tumor development. These changed genes are known as oncogenes, because they induce the oncogenic state — cancer. Oncogenes are dominant, because a change/mutation of only one of the cell’s two copies of that gene can lead to tumor formation. nullThe basic concept 2 proto-oncogenes: The normal precurcers of these above genes are termed proto-oncogenes and are essential for normal cell growth and differentiation. proto-oncogenes is also called as cellular oncogenes. 3 virus oncogene: these genes are in viruses, may leading to uncontrolled cell proliferation and tumor development. Virus oncogenes are homolog with that corresponding cellular oncogenes. nullThe basic concept 4 cancer suppressive genes: These genes code for proteins whose normal function is to turn off cell growth. A change/mutation in one of these growth-limiting genes may result in a protein product that has lost its growth limiting ability. The normal forms of such gense have been shown to suppress tumor growth and are known as tumor suppressor genes or anti-oncogenes as well. Because both cellular copies of a tumor suppressor gene must be mutated to foil its growth-limiting action, these genes are recessive in nature.nullFig. 20-1 Structure of RSV genome9392 bpLTRLTRgagpolenvsrctyrosine kinase 526 residue 60 kDwide type viral genesoncogeneto initiate and regulate transcriptionnullThe pp60V-SRC is anchored to the plasma membrane via an N-terminal myristyl groupnullnullMechanism on oncogene activated to obtain a strong promoter or enhancer. gene translocation. protooncogene amplification in the genome. point mutationto obtain a strong promoter or enhancer.nullavian leukemia virus genomehost cell genomessRNAdsDNAc-mycLTRto increase c-myc gene expression, 30-100 times, compare with no infection.nullMechanism on oncogene activated to obtain stronge a promoter or a enhancer. gene translocation. protooncogene amplification in the genome. point mutationnullnullMechanism on oncogene activated to obtain stronge a promoter or a enhancer. gene translocation. protooncogene amplification in the genome. point mutationnullnullMechanism on oncogene activated to obtain stronge a promoter or a enhancer. gene translocation. protooncogene amplification in the genome. point mutationnullGGCGTCH-rasGlyValDNAProteincarcinomanormalnullnullnullnullnullPhospho- rylation sitenullnullnullnullnulltumor suppressor genes two examples Rb: 13q14.1-14.2, 27 exon, complete length 180 kb, mRNA 4.7 kb, encoding protein 105 kD, 928 residues, locate in nucleus, inactive form: phosphorylation Rb, active form: non-phosphorylation Rb, be able to bind activated transcription factor E-2F, be able to inhibite RNA polymerase I and RNA polymerase III . p53: 17p13, 11 exon, complete length 16-20 kb, mRNA 2.8 kb, encoding protein 53 kD, 393 residues, locate in nucleus, is phosphorylated, tetramer.nullnullnullSummary The basic concept: oncogene, proto-oncogene, virus oncogene, tumor suppressor gene Mechanism on oncogene activated Function of oncogene and tumor suppressor gene null选择题练习 癌基因与抑癌基因null1. 细胞原癌基因A 正常人细胞也检测到的癌基因 B 只在肿瘤细胞中出现 C 加入化学致癌物到正常细胞后才出现 D 是细胞经过转化才出现 E 感染致癌病毒才出现null2. 关于细胞癌基因,正确的叙述是A 存在于RNA病毒中 B 存在于DNA病毒中 C 存在于正常细胞基因组中 D 正常细胞出现可导致肿瘤 E 只存在于肿瘤细胞细胞null3. 致癌病毒A 使人体直接致癌 B 使正常细胞转化为癌细胞 C 均为DNA病毒 D 均为RNA病毒 E 含转化酶null4. 不属于癌基因产物的是A 化学致癌物 B 生长因子类似物 C 结合GTP的蛋白质 D 结合DNA的蛋白质 E 酪氨酸蛋白激酶null5. 有关抑癌基因,错误的叙述是A 能抑制细胞的分化 B 能抑制细胞过度生长 C 突变后可导致肿瘤形成 D 可诱导细胞凋亡 E 最早发现的抑癌基因是Rbnull6. 有关P53蛋白,错误的描述是A 其基因位于17p13, 突变后可致癌 B 能引发修复失败的细胞程序自杀 C 有“基因卫士”的称号 D 有转录因子作用 E 能激活解链酶null7. 有关Rb基因,错误的描述是A 位于13q14 B 是一种抑癌基因 C 其作用与E-2F有关 D 其编码蛋白为P21 E 突变后可导致肿瘤发生null8. 关于凋亡,正确的叙述是A 是一种病理过程 B 是细胞坏死 C 由意外事件引起的细胞损伤造成 D 由基因控制的细胞自我消亡的过程 E 与癌基因的表达调控无关null9. 生殖细胞抑癌基因的突变可引起A 生殖功能障碍 B 各种先天性的肿瘤 C 家族性的肿瘤易感性 D 后代的发育正常 E 家族性癌症发病率下降null10. 使癌基因活化的因素有A 正常基因表达增强 B 正常基因表达减少 C 抑癌基因表达增强 D 细胞增殖、分化加强 E 点突变null11. The oncogene which can encode epidermal growth factor receptor isA src B ras C myc D sis E erb-Bnull12. The oncogene which can encode GTP binding protein isA src B ras C myc D sis E erb-Bnull13. The oncogene which can encode protein having TPK activity isA src B ras C myc D sis E erb-Bnull14. Which isn’t a anti-oncogene?A P16 B P53 C Rb D WT1 E H-rasnull 15. 正常基因的异常表达可致A 细胞形态改变 B 细胞癌变 C 异常表型 D 细胞结构与生物活性改变 E 细胞凋亡null 16. 细胞癌基因可在下列情况下激活A 基因发生突变 B 有化学致癌剂存在 C 有病毒感染 D 生长因子与DNA互相结合 E 受体激活null 17. 野生型P53基因是抑制基因 一定情况下,能启动细胞自杀 编码蛋白有转录因子作用 能抑制解链酶活性 与复制因子A相互作用,参与DNA的复制与修复null 18. Rb基因的特点A 位于13q14 B 含27个外显子 C 编码产物 105KD D 转录产物 4.7kb E 全长 20 kbnull 19. Which is oncogene expression product?A GTP binding proteins B DNA binding proteins C tyrosine protein kinase D growth factors E cytoskeletal proteinsnull 20. The activation ways of proto-oncogene are A point mutation B gene translocation C gene amplification D protein phosphorylation E obtaining promoter