1963? Abelev AFP

1
??????????
??? ????????

• ?1??(1963-1978)?????
• 1963? Abelev AFP
• 1965? Gold Freeman CEA
• ?2??(1979-1989)??????
• 1980? Koprowski CA19-9(1116-NS-19-9)
• 1981? Bast et al CA125(OC125)
• ?3??(1990??)????
• ??????

2
???????????
1910 Rous ???? ?????
1960 Huebner ??????
1970 Martin Rous??src??
1976 Bishop ????(V-src)???? 1989 Nobel
1986 Dryja ????????Rb
1987 Lee ????
1988 Steeg ???????? nm23 ?????
1989 Ebralidze ?????? mts1 ?????
3
??????? ???? ???? ?????????
(virus oncogene,v-onc)??????? (cellular
oncogene,c-onc) ???? (suppressor gene)
4
???? ? ?????? ? GTP? ? ???? ? ??? ? DNA??
5
???????????????? ??????????????,????
??????????? ???????????,?????,?
???(apotosis)?????
???????????,???????????????????,??????,???????
??????????????,??????????????????
6
?????(oncogene,onc)?????????1???
??????????(v-onc)??????(c-onc)??,????????????????
??? ? ? ?
7
2???(1)v-onc???????????????,?
??????(2)c-onc????????????????,
?????????????????,? ??????,????????????
?????,???????,????? ????????
8
(3)?????? ?3?????????,?ras?src?myc?
??????????????v,?v-ras,??????????????c,?
c-ras?
9
(?)????? ????????Rous????(Rous sarcoma
virus,RSV)??????????????
10
Point mutations identified in human tumors
11
Oncogen amplification in human tumors
SCLC small cell lung carcinoma
12
Chromosomal translocations commonly occurring in
human tumors
13
??????,????????,???????????????,?????????,????
????
14
(?)????? ???????????,????????????????????????
??????????????(c-onc) ?????(proto-onc)?
15
???????????????????????DNA???????,??????????
16
??????????????????????,??????????????
???????
17
1?sis?? ????,?c-sis ?????22????,5?????
?241????????(p28)???????????????(PDGF)?
87????,??PDGF?????
18
??PDGF???????????????? ???,?c-sis???PDGFR,?
??? ????????
19
2.erb?? ?????????????????????????????????????
???????????????
20
?erb-B?????????????(EGF)??,??????????-????????
??,???????????????????
????????,???????,????????,?????????????????
21
(No Transcript)
22
3.src?? ?? c-src????20????,17??????
60kDa????,???????? (tyrosine protein
kinase,TPK)????????250????????????,
????????TPK??? ????????????,???????
?,??????????,????? ???????,??????????
??
23

24
4.ras?? ??H-ras?K-ras?N-ras
H?K-ras??????????Harvey?Kirsten?
N-ras????????(neuroblastoma)??? ??4??????,
????21Kd???????????85????,??
?????????,?G????????????????????,??
?????????????????
25
ras?GTP????????,GTP???,ras?GDP???????????
26
(No Transcript)
27
(No Transcript)
28
5.myc???myb?? ??c-myc,N-myc?L-myc?R-myc??3??
????,Exon1???,??ATG,? ????????????????62-
64kDa?66-67kDa??? ??????,??DNA?????,?DNA??
???? myb?????????????????,?????????????????
??????????????????????,?
?????DNA???,??DNA????? ??????????,????????
?????????????
29
(No Transcript)
30
(No Transcript)
31
??????????? ?????????????,???????????,????????
??????????? ???? ???? ?????
????
32
(?)???????(point mutation) ???????????????????
??????,??????????????????,?????????????
33
(No Transcript)
34
(?)?????????????? ????????????????????mRNA????
??????????? ???????????????????????????,??????
??? ?????????5?????????(1ong terminal
repeat,LTR)????????????????????,?????,????????????
???????????
35
(No Transcript)
36
(No Transcript)
37
(?)??????????????
DNA???????(methylation)???????????????
38
???????????????????,ras???DNA??????????????????,??
????????????????????
39
(?)??????????????(amplification)
?????????????????????????,?????????????,?????????,
?????????????? ????????N-myc???10-200?,???
mRNA?????????????
40
(No Transcript)
41
(No Transcript)
42
(?)?????????????? ????(translocation)????(r
earrangemant) ????????????????????????????,??
????????,???????????????,??????????????????????
43
?c-myc?????8q24,????IgH(???14q32)?lg?
(???2p12)?Ig?(???22q11)?????????,??????c-myc??????
???????,??c-myc??,?c-myc??????,??????,??????????
44
????????9q34?c-abl??????22?????,????bcr-abl???
?,?????,???????p145??p210,??????????????,?????????
?????
45
??? ???? ????(suppresser
gene)??????(anti-onc),??????????????????????,?????
????????????????????,??????????????????
46
(No Transcript)
47
???????????? ??????????????????,??????????????
???????,?????????????????????
48
??????????1????????(retino-blastoma,Rb)(1)????
???27????,3-17???????
?????????????p105????,????DNA???,?
????????????????
49

(2)?? ????????,???p105???????????????Rb??????
?,?DNA??????????????Rb?,Rb????????,????????????,??
???
50
RB--tumor suppressor
RB phospholation release cycle block
RB dephospholated
P
P
RB
P
RB
P
RB phospholated
P
P
E2F
RB
E2F released activates transcription
RB binds E2F blocks G1/S transition
E2F
Represses target genes
51
??????????????Rb????????,??Rb??????????????Rb???,
????,????????????,?????????,????????Rb
mRNA??????????,??????Rb????
52
????????????
??1 ??2 ???? M
W ?? ???? M W M
M ??
53
(2)p53?????17p13,11????,10???????393????,p53
54
????????DNA??????(1)?????????????????S???DNA????
????
55
(No Transcript)
56
(No Transcript)
57
???p53???? p53??bcl-2???bax,????????????p53??
?????????????p53?????????
58
????p53??249?G ? T
59
DNA damage
?p53
60
?.?????????? (?)?????? ?????????????
????(??????????) ????(??????)
????(DNA?RNA????) ?????????????????
61
1????? ??????? ???DNA???????,??????????
?? ????????????,??????????,?????????????????
???????????????????
62
2????? ?????(?????DNA?????)
????????????????,?????????,??????????
63
3????? ?????????????????????????????????????
??
64

2
3
1
4
5
65
??? ????????????????????????????????5-6????
?? ?ras??? ?????????????(FAP)???
???(DCC)??? ? c-myc??????? ? p53???????????,???
??????????
66
(No Transcript)
67
(No Transcript)
68
(?)???????1?ras?????2.myc?????
69
(?)???????1?Rb?????2?p53????? 3???
BRCA1?BRCA2??????????????,?????????????
70
??? ???????????????

• ????
• ???? PCR, RT-PCR
• ???? DGGF (????????)
• ???? Southern blot , Northern blot, FISH
• ??????
• ???????
• ??? ????,ELISA, RIA

71
??????1?PCR/ASO???(PCR-allele-specific
oligonucleotide ??????????,???????????????????
,???????????????
72
2???????????(RFLP)??
73
3?PCR-SSCP???? ???????,???DNA???????????,???????
?,?????ras???????????????????,????????????????????
,???????????????????,?????????????
74
4?Southern Blot
75
Single-color FISH
double-color FISH
76
????
Stanford ??????(Perou et al.1999)
77
?????????????????? ????????????????????,????
?????Rb???????????APC?????????,???????????????????
? ???????????????????
78
???????????

• ?????????c-myc?c-fos?H-ras?k-ras
• ?????????c-abl?c-sis
• ????????c-mos?cyes?cfps?c-sac?
• ???abl?ras
• ???????c-myc
• ???,???,??ras
• ???,???BRCA1?c-erbB-2

79
???????????
??????????
1) Oncogene amplification neuroblastoma N-myc,
C-erb-B2 2) Oncogene overexpression small
cell lung carcinoma C-myc 3) Oncogene mutation
bladder cancer H-ras 4) Suppressor gene
deletion retinoblastoma RB gene
80
?????
???? ??? ????? ???? ???? ???
??? 1????????????? 2??????????
81
(No Transcript)