Chapter 16 oncogene anti oncogene and growth factor
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Chapter 16 Oncogene, Anti-oncogene and Growth Factor. 第十 六 章 癌基因、抑癌基因与生长因子. 引言. 据估计,大约有三分之一的人在生命的某一阶段要遭遇癌症。 迄今发现的癌症有 200 多种,我国最为常见和危害性最严重的肿瘤为 肺癌、食管癌、胃癌、大肠癌、肝癌、乳腺癌、鼻咽癌、宫颈癌和淋巴瘤、白血病 。 根据卫生部肿瘤防治办公室提供的 2006 年我国肿瘤发病率和十大恶性肿瘤发病率排序显示, 肺癌 、 乳腺癌 分别位居 男、女性恶性肿瘤发病首位 ,男女恶性肿瘤 死亡率最高 的均为 肺癌 。.

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Chapter 16 Oncogene, Anti-oncogene and Growth Factor

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Chapter 16 oncogene anti oncogene and growth factor

Chapter 16 Oncogene, Anti-oncogene and Growth Factor


Chapter 16 oncogene anti oncogene and growth factor

  • 200

  • 2006


Chapter 16 oncogene anti oncogene and growth factor

  • tumor


Chapter 16 oncogene anti oncogene and growth factor


Chapter 16 oncogene anti oncogene and growth factor

(Oncogene)


Peyton rous and rous sarcoma virus

Peyton Rous and Rous sarcoma virus


1966 g

1966 G.

  • 1910

  • 30()


Chapter 16 oncogene anti oncogene and growth factor

  • 1932Shope


Chapter 16 oncogene anti oncogene and growth factor

  • 1950

  • Rous(acute transforming retrovirusRNA)


Chapter 16 oncogene anti oncogene and growth factor

Rous

196687


Chapter 16 oncogene anti oncogene and growth factor

  • Bishop1980

  • Rousv-onc


Chapter 16 oncogene anti oncogene and growth factor

Virus-like particles assembled in vitro with purified Rous sarcoma virus Gag protein


Chapter 16 oncogene anti oncogene and growth factor

LTR

gag

pol

env

src

LTR

* RSV, Rous sarcoma virus

  • LTR (long terminal repeat)DNA

  • srcRSV


Chapter 16 oncogene anti oncogene and growth factor

LTR

LTR

GAG

POL

ENV

LTR

ONC

LTR

GAG

POL

ENV

  • v-onc)


Chapter 16 oncogene anti oncogene and growth factor

RNA

RNA

RNA-DNA

RNA

Proto-oncogenes

DNA

DNA

RNA-


Chapter 16 oncogene anti oncogene and growth factor

    • virus oncogene,v-onc

    • (cellular-oncogene, c-onc)proto-oncogene, pro-onc


Chapter 16 oncogene anti oncogene and growth factor

  • (house-keeping gene)

    • ;


V onc c onc

v-oncc-onc

  • v-onc

  • v-oncc-onc

  • v-onc


Chapter 16 oncogene anti oncogene and growth factor


Chapter 16 oncogene anti oncogene and growth factor

  • (1) srcavian Rous sarcoma virusRous

    • erbavian erythroblastosis virus

    • sissimian sarcoma virus

    • rasrat sarcomas

  • (2) 3

  • erbA--

  • erbB--


Chapter 16 oncogene anti oncogene and growth factor

  • src

  • ras p21GTPGTP

  • myc DNA

  • sis p28(

  • erb

  • myb


Chapter 16 oncogene anti oncogene and growth factor

1GFPDGFEGFTGF-2

2

3

4


Chapter 16 oncogene anti oncogene and growth factor


Chapter 16 oncogene anti oncogene and growth factor

1982 3 EJ c-H-ras356

1 2 3 4 5 6 7 8 9 10 11 12 13 14

H-rasATG ACG GAA TAT AAG CTG GTG GTG GTG GGC GCC GGC GGT GTG

H-ras ATG ACG GAA TAT AAG CTG GTG GTG GTG GGC GCC GTC GGT GTG

p21Met Thr Glu Tyr Lys Leu Val Val Val Gly Ala Gly Ala Val

p21 Met Thr Glu Tyr Lys Leu Val Val Val Gly Ala Val Ala Val


Chapter 16 oncogene anti oncogene and growth factor

  • Ras

GDP

GTP

Pi

Ras

GTP

GDP-GTP

Ras

Ras

GDP

GTP


Chapter 16 oncogene anti oncogene and growth factor

  • HarreyKirfenH-rasK-rasN-ras12136112


Chapter 16 oncogene anti oncogene and growth factor

GC GC GC

GCAC AT

CG CG CG

12

O6

p21


Chapter 16 oncogene anti oncogene and growth factor

  • DNAc-mycc-myc


Chapter 16 oncogene anti oncogene and growth factor

avian leucosis virusALV

c-myc

exon-3

exon-1

exon-2

exon-3

exon-1

exon-2

LTR

LTR

ALV

DNALTR

c-myc

exon-3

exon-2

LTR

exon-1

ALV

c-myc30-100

exon-3

exon-2

exon-1

LTR

ALV


Chapter 16 oncogene anti oncogene and growth factor

  • DNA5%


Chapter 16 oncogene anti oncogene and growth factor

DNA

      • DNA

  • DNA

  • DNA


Chapter 16 oncogene anti oncogene and growth factor


C myc

c-myc

  • c-mycALV

  • c-mycG0G1c-myc

  • c-mycc-myc

  • 1985Shibuyac-myc


Chapter 16 oncogene anti oncogene and growth factor

    • 1960NowellHungeforaPhiladelphia chromosome, Ph

    • Ph


C abl

c-bcr

c-abl

c-ablbcr

c-abl


Chapter 16 oncogene anti oncogene and growth factor

  • 2008121


Chapter 16 oncogene anti oncogene and growth factor

Section 2 Anti-oncogene


Chapter 16 oncogene anti oncogene and growth factor

  • anti-oncogene


Chapter 16 oncogene anti oncogene and growth factor


Chapter 16 oncogene anti oncogene and growth factor

  • 23

    • Rbretinoblastoma

    • Bcl-2B-cell lymphoma B

    • p5353KD

    • p

    • ras: Ras, p21


Chapter 16 oncogene anti oncogene and growth factor


Chapter 16 oncogene anti oncogene and growth factor

retinoblastoma gene,Rb


Retinoblastoma rb

retinoblastomaRb

  • 2


Chapter 16 oncogene anti oncogene and growth factor

1. Rb

  • Rbretinoblastoma gene

  • 1986

  • Rb 13q14200kb2726mRNA4.7kb,105-110kDp105-RB


Chapter 16 oncogene anti oncogene and growth factor

2. Rb


Chapter 16 oncogene anti oncogene and growth factor

DNA

Rb

P

DNA

G0 G1

Rb

E2F

cyclin dependence protein kinase, CDK)

S

E2F

mRNA


P105 rb

Rb

E-2F

P

P105-Rb

G0 G1

DNA

Rb

S

E-2F

DNA

mRNA


Chapter 16 oncogene anti oncogene and growth factor

RB

  • DNARBRB

    • E1ASV40TE7


Chapter 16 oncogene anti oncogene and growth factor

p53

  • cancer suppressive gene ;

  • Pubmed4;

  • 50%p53;

  • 1989.


Chapter 16 oncogene anti oncogene and growth factor

P53

DNA

DNA

p53

  • p5320kb17p131139353kd;

  • P53NC


Chapter 16 oncogene anti oncogene and growth factor

p53

  • p53 DNA


Chapter 16 oncogene anti oncogene and growth factor

p53

p53p2121kDp21WAF1/CIP1p21CDKG1

DNA

DNA p53G1DNA


Chapter 16 oncogene anti oncogene and growth factor

DNA

  • p53A(RPA)

  • p53RPARPADNAS

  • p53DNA

  • p53 G1DNA


Chapter 16 oncogene anti oncogene and growth factor

p21

p53

A

p53

DNA

p53

p53

p21

G1


Chapter 16 oncogene anti oncogene and growth factor

p53

5-8


Chapter 16 oncogene anti oncogene and growth factor

<Humphrey)

1967


Chapter 16 oncogene anti oncogene and growth factor

P53

1994PCR1967p53

p53227


Chapter 16 oncogene anti oncogene and growth factor

  • MycRas


Chapter 16 oncogene anti oncogene and growth factor

ER FearonB Vogelstein , 1990


Chapter 16 oncogene anti oncogene and growth factor

APC

  • APC1986Herrera5q212843

  • Dihlmann500(familial adenomatous polyposisFAP)APC8OAPC

  • APC


K ras

K-ras

  • K-ras

  • GTP

  • 5O%K-ras

  • K-ras


Chapter 16 oncogene anti oncogene and growth factor

p53

  • p5317pl3

  • l7p53p53

  • 17


Point

point

    • Rbp53


Chapter 16 oncogene anti oncogene and growth factor

  • p53


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