??????COX-2???????????

1
??????COX-2??????????? ??????????? Aberrant
methylation and histone deacetylation
of cyclooxygenase 2 in gastric cancer.
International Journal of Cancer 2002, 97 272-277
??????? ?? ??
2
?????
COX-2????????80??????????????????????????????????
????
NSAIDs?COX-2???????????????? 40
??????????????????????????????????????????????????
????????
COX-2 ????
?? ??
MMP-2 ????
???? ????
??? ??
PGE2 ??
E-cadherin ????
?????? ????
3
COX-2 ??????????
EGF -R
p53
MAPK
?????
????
COX-2
COX-2 ???????growth factor ?? oncogenic ? signal
??????p53 ??? anti-oncogenic ? signal ????????????
4
?????
COX-2?????????????????????????????????????????????
COX-2?????????????CpG ??????????COX-2???????????Cp
G??????????????
??????????????????????????????????????????????????
?????COX-2??????????????????????????????
5
COBRA (COmbined Bisulfite Restriction Analysis )
????
5m
bisulfite PCR
Restriction electrophoresis
TCACAGAG CGG
sodium bisulfite
5m
GCA C
TUAUAGAGCGG
GTAC
PCR
0 50 100 Methylation
Afa I site
TTATAGAGCGG
????????? COBRA ???DNA?Bisulfite??????????????????
???????????????????????????????????????Bisulfite??
??DNA?PCR?????????????????????????????????????????
?????
6
????????? COX-2 ??????????
CpG
Exon 1
100 bp
AfaI
23164 bp
COBRA
TaiI
2350114 bp
AfaI
TaiI
COBRA ????????????????? M ??????????? U
???????Afa I , Tai I ????????????????MKN28?KatoIII
????????????????? 8 ?? 2 ? ( 25
)????????????????RKO ? Positive control ???????
7
????????? COX-2 ??????????
Bisulfite-Sequence
A
A/T
A
A/T
CpG
CpG
MKN 7
MKN 28
MKN 45
KATO III
Bisulfite