Download 2-14 oncogene and suppressive gene of cancer-xu liyan

Oncogene
Cancer suppressive gene
Liyan Xu
The 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.
The 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.
The 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.
Fig. 20-1 Structure of RSV genome
9392 bp
wide type viral genes
LTR
gag
to initiate
and regulate
transcription
pol
oncogene
env
src
LTR
tyrosine kinase
526 residue
60 kD
The pp60V-SRC is anchored to the plasma membrane via an
N-terminal myristyl group
Fig. 20-2 Integration of RNA virus genome and host cell genome
RNA virus
host cell
virus RNA
provirus DNA
+
c-onc.
v-onc.
+
+
Mechanism on oncogene activated
 to obtain a strong promoter or enhancer.
 gene translocation.
 protooncogene amplification in the genome.
 point mutation
avian leukemia
virus genome
ssRNA
host cell
genome
LTR
c-myc
dsDNA
to increase c-myc gene expression, 30-100 times,
compare with no infection.
Mechanism on oncogene activated
 to obtain stronge a promoter or a enhancer.
 gene translocation.
 protooncogene amplification in the genome.
 point mutation
Burkit lymphoma
14 chromosome
IgH gene regulation region
8 chromosome
c-myc
t（8:14）
to increase c-myc gene expression obviously
Mechanism on oncogene activated
 to obtain stronge a promoter or a enhancer.
 gene translocation.
 protooncogene amplification in the genome.
 point mutation
ras or c-myc
amplification
1
2
3
n
expression of ras or c-myc is increased obviously
Mechanism on oncogene activated
 to obtain stronge a promoter or a enhancer.
 gene translocation.
 protooncogene amplification in the genome.
 point mutation
H-ras
DNA
normal
GGC
Protein
Gly
Val
carcinoma
GTC
418
Fig. 20-3 Oncogene and signal transduction for growth
EGF
SIS
erbB-2
PDGF receptor
SRC
AC
cAMP
kinase kinase
RAS/Gpro.
PLA2
PKA
extracellular
PLC
PIP2
membrane
DG
PKC cytoplasm
AA
+
IP3
PG
ER
Ca2+
effects
targets targets targets
effects
DNA
mRNA
kinase
RNA pol.
targets
nucleus
418
Fig. 20-3 Oncogene and transduction of information for growth
EGF
SIS
erbB-2
PDGF receptor
SRC
AC
cAMP
kinase kinase
RAS/Gpro.
PLA2
PKA
extracellular
PLC
PIP2
membrane
DG
PKC cytoplasm
AA
+
IP3
PG
ER
Ca2+
effects
targets targets targets
effects
DNA
mRNA
kinase
RNA pol.
targets
nucleus
Phosphorylation site
418
Fig. 20-3 Oncogene and transduction of information for growth
EGF
SIS
erbB-2
PDGF receptor
SRC
AC
cAMP
kinase kinase
RAS/Gpro.
PLA2
PKA
extracellular
PLC
PIP2
membrane
DG
PKC cytoplasm
AA
+
IP3
PG
ER
effects
DNA
mRNA
kinase
Ca2+
effects
targets targets targets
Ca2+
RNA pol.
targets
nucleus
418
Fig. 20-3 Oncogene and transduction of information for growth
EGF
SIS
erbB-2
PDGF receptor
SRC
AC
cAMP
kinase kinase
RAS/Gpro.
PLA2
PKA
extracellular
PLC
PIP2
membrane
DG
PKC cytoplasm
AA
+
IP3
PG
ER
Ca2+
effects
targets targets targets
effects
DNA
mRNA
kinase
RNA pol.
targets
nucleus
tumor 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: nonphosphorylation 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.
cell DNA damage
p53 
damaged DNA repair
repair is unsuccessful by p53
cell apoptosis
repair is successful by p53
cell survive
Oncogene and tumor suppresor gene

Our experiment result about the oncogenes and tumor
suppressor genes for esophageal cancer
human papilloma virus
E6 and E7 genes
normal
embryo
esophageal
epithelial
cell
12-o-tetradecanoylphorbol
-13-acetate,TPA carcinogen
plasmid
transfection
immortal
esophageal
cell
canceration
esophageal
cancer cell
cDNA array
up clone: 33
down clone: 28
suppression
subtractive
hybridization
up clone :62
down clone:56
mRNA difference
down
up
difference cDNA clone
Summary

The basic concept: oncogene, proto-oncogene, virus oncogene,
tumor suppressor gene

Mechanism on oncogene activated

Function of oncogene and tumor suppressor gene
选择题练习
癌基因与抑癌基因
1. 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
2. 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
3. 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
4. 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
5. 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Rb
6. 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
7. 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
8. 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
9. 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
10. 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
11. The oncogene which can encode epidermal
growth factor receptor is
A src
B ras
C myc
D sis
E erb-B
12. The oncogene which can encode GTP binding protein is
A src
B ras
C myc
D sis
E erb-B
13. The oncogene which can encode protein
having TPK activity is
A src
B ras
C myc
D sis
E erb-B
14. Which isn’t a anti-oncogene?
A P16
B P53
C
Rb
D WT1
E
H-ras
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
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
17. 野生型P53基因
A. 是抑制基因
B. 一定情况下,能启动细胞自杀
C. 编码蛋白有转录因子作用
D. 能抑制解链酶活性
E. 与复制因子A相互作用,参与DNA
的复制与修复
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 kb
19. Which is oncogene expression product?
A GTP binding proteins
B DNA binding proteins
C tyrosine protein kinase
D growth factors
E cytoskeletal proteins
20. The activation ways of proto-oncogene are
A point mutation
B gene translocation
C gene amplification
D protein phosphorylation
E obtaining promoter