癌基因与抑癌基因

膜内侧
myc家族：c-myc、N-myc、L-myc 结合蛋白 核内 jun、 fos 转录因子（AP-1） 核内 sis家族： 仅sis P28(类PDGF) 胞外 myb家族：myb、myb-ets 核蛋白(转录因子) 核内
2、based on function and location
类 别 生长因子 生长因子受体 名称 c-sis c-erb B c-fms 定位 分泌到胞外 细胞膜 细胞膜 生物学功能 血小板源生长因子 表皮生长因子受体 集落刺激因子-1受体
OVERVIEW
• Many genes and factors outside of genes is involved in carcinogenesis. The accumulation of many genetic changes cause cancer other than mutations of a single gene by causing disorders of cell growth and differentiation, the cell proliferation out of control. • Oncogene, antioncogene, tumor metastasis gene, cell apoptosis, DNA damage and repair, telomerase, microRNA
Pi
GTPase activating protein,GAP
GDP
Inactive Ras protein
Relationships of oncogene, tumor suppressor gene and growth factors
tumor suppressor gene Negative regulation
cells
Positive regulation
oncogene
products
2、Proto-oncogenes or cellular-oncogene, c-onc: the oncogenes existing in normal genome which are in quiescence or inactive state such as c-myc、c-ras、c-src。Under normal condition， these genes are in quiescence or low expression state and not only no harmful to cells but also helpful to stain normal function to cells.
c-trk
胞内传递蛋白
细胞膜
神经生长因子受体
酪氨酸蛋白激酶 Ser/Thr蛋白激酶
c-src、c-abl 细胞质 c-raf、c-mos 细胞质
c-ras
转录调节因子 c-myc c-jun、c-fos c-erb A
细胞膜
细胞核内 细胞核内 细胞核内
GTP/GDP结合蛋白
DNA结合蛋白 转录因子（AP-1） 甾体激素受体类蛋白
Section I Oncogene
• • • • Concept of oncogene Viral oncongene Cellular oncogene The products of oncongene and its fuction
一、the concept of oncogene
Oncogene：the genes in cells is responsible of controlling cell growth, proliferation and differentiation. They will cause cellular canceration when their structure or expression turns abnormal. All of genes which encode for growth factors, growth factor receptors, signal molecules and transcription factors related to growth.
The proto-oncogenes are point mutated by exposure Fra Baidu bibliotekf radiation and carcinogens, the amino acid
or the structure of protein is changed and the protein is in continuous active state, which lead to carcinogenesis. 1982, MIT University, National Cancer Institute and Columbia University：human
Voiceover : that is why such RSV retrovirus induce host cell carcinogenesis.
三、cellular oncogene
the oncogenes existing in normal genome which are in quiescence or inactive state such as c-myc、c-ras、csrc。Under normal condition，these genes are in quiescence or low expression state and not only no harmful to cells but also helpful to stain normal function to cells.
Growth factor •
The regulation of gene expression and cell proliferation, differentiation is involved in the
mechanism of oncogenes and tumor suppressor
Rous Peyton
Rous 肉瘤
1970,Temin and Batimore, reverse transcriptase，1975 Nobel
1971, Duesberg, the genome of RSV
Normal virus gene
5’
LTR gag pol env
oncogene
The writing of oncogene
ras、src、myc
v-ras
c-ras
Classification of oncogene
1、virus oncogenes，v-onc: the genes existing in virus (mostly, retrovirus) which cause the target cells maligant transformation, such as v-src
c-H-ras H-ras GGC (12Gly) GTC (12Val)
bladder cancer results from the point mutation of
normal cells
turmor cells
the protein of mutated ras is locked in active state
（一）the traits of cellular oncogene
Universality ：exists in biological widely；
conservatism ：The gene sequence was highly homologous in the process of evolution Importance ：the expression protein regulate cell proliferation, differentiation and apoptosis precisely Harmfulness: the variation of structure and numbers make cell carcinogenesis
四、activation of oncogene
Activation factors：oncogene is activated and abnormal expressed under some conditions such as virus infection, exposure to chemical carcinogen or ionizing radiation, leading to cell malignant transformation and carcinogenesis. Different cellular oncogenes under different condition can be activated by different pathway and become ‘active oncogene’. The results of oncogene activation will be （1）The expression product is abnormal or truncated （2）the products are normal but excessive （3）new products appear
1979, H. Varmus and J. M. Bishop found that src is carcinogenesis in RSV, but also found that the homologs of src exist in animal cells commonly if the cDNA of src is hybridized with other genome DNA. Result: src stem from normal cell genome. ----- 1989 Nobel
（二）the classfication of cellular oncogene
1. Based on family
family member action src家族： src、abl、fgr、fes、 TPK活性 yes、fps、 lck、kek、（酪氨酸蛋 fym、lyn、tkl 白激酶） ras家族： H-ras、K-ras、N-ras G蛋白( P21) location 膜内侧或跨膜
3’ src
LTR
regulating and initiating transcription
the core protein of virus
reverse transcriptase and Integrase
Outer membrane protein
Tyrosine kinase
the structure of Rous sarcoma virus
The structural comparison of c-src and v-src
二、Virus oncogenes
the oncogene existing in virus genome which does not encode the protein of virurs and is not helpful to replication but do make host cell Continuous proliferation
Activation mechanism：Gene mutation, gene amplification, chromosomal rearrangements, variation of oncogene methylation gene overexpression etc.
（一）point mutation