《现代分子生物学》疾病和人类健康.ppt

（3）抑癌基因产物对原癌基因的调控(p53,Rb) （4）外源信号对原癌基因表达的影响 第一节 肿瘤与癌症 内容提要： 癌基因(oncogene) 反转录病毒致癌基因 细胞转化基因 抑癌基因(tumor suppressor gene ) 二、抑癌基因 抑癌基因(tumor suppressor gene ) /隐性癌基因：是一种抑制细胞生长和肿瘤形成的基因。如：Rb抑癌基因、抑癌基因p53 抑癌基因与原癌基因在生物学上有以下几点差异： ①在功能上，抑癌基因起负调控作用，而原癌基因起正调控作用； ②在遗传方式上，原癌基因是显性的，而抑癌基因在细胞水平上是隐性的， ③在突变发生的细胞类型上，抑癌基因突变可以发生在体细胞中，也可能发生在生殖细胞中并通过生殖细胞得到遗传。原癌基因突变只发生在体细胞中。 癌症的多阶段发生学说 (multi-stage) 肿瘤与癌症 人免疫缺损病毒——HIV 乙型肝炎病毒——HBV Contents 第二节 人免疫缺损病毒——HIV HIV病毒粒子的形态结构 HIV基因组及其编码的蛋白 HIV的复制 P24 Capsid protein P18 Matrix protein 一、 HIV病毒粒子的形态结构 二、HIV基因组及其编码的蛋白 编码病毒的核心蛋白 编码反转录酶、整合酶和蛋白酶 编码外膜蛋白 TAT and REV are essential for HIV replication GAG gene-p55 p17: inner surface p24: nucleocapsid p9: nucleocapsid associated with RNA Polymerase (reverse transcriptase) 2. Integrase 3. Protease (cuts polyproteins) POL gene Membrane: host derived Two glycoproteins: gp160 gp120 and gp41 gp41 is fusogen that spans the membrane gp120 gp41 ENV Gene coding 三、HIV的复制 The Life Cycle of HIV 1. Virus destroys the cell as a result of budding 肿瘤与癌症 人免疫缺损病毒——HIV 乙型肝炎病毒——HBV Contents 二、 HBV的复制 dsDNA,不是通过半保留复制方式复制 Cellular proto-oncogenes have been found in multiple copies in various tumors and transformed cell lines. The amplified proto-oncogene copies can occur in homogeneously staining chromosomal regions or double-minute chromosomes. The mechanism of gene amplification is not fully understood, illegitimate DNA replication occurring more than once during a single cell cycle could account for the increase of multiple segments (amplification units) of DNA from 200 to 2000 kb in size. All amplified proto-oncogenes express high levels of the corresponding RNA and protein and appear to be unrearranged. The amplified proto-oncogene is frequently tumor-specific; for example, N-myc or c-myc may be associated with the progression of neuroblastomas and small cell lung carcinoma cells. This suggests that increased expression of these proto-oncogenes plays a role in the deve