SUPPRESSION OF INTESTINAL NEOPLASIA BY DNA HYPOMETHYLATION

被引：639

作者：

LAIRD, PW

JACKSONGRUSBY, L

FAZELI, A

DICKINSON, SL

JUNG, WE

LI, E

WEINBERG, RA

JAENISCH, R

机构：

[1] MIT,DEPT BIOL,CAMBRIDGE,MA 02142

[2] MASSACHUSETTS GEN HOSP E,CARDIOVASC RES CTR,BOSTON,MA 02129

来源：

CELL | 1995年 / 81卷 / 02期

关键词：

D O I：

10.1016/0092-8674(95)90329-1

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

We have used a combination of genetics and pharmacology to assess the effects of reduced DNA methyltransferase activity on Apc(Min)-induced intestinal neoplasia in mice. A reduction in the DNA methyltransferase activity in Min mice due to heterozygosity of the DNA methyltransferase gene, in conjunction with a weekly dose of the DNA methyltransferase inhibitor 5-azadeoxycytidine, reduced the average number of intestinal adenomas from 113 in the control mice to only 2 polyps in the treated heterozygotes. Hence, DNA methyltransferase activity contributes substantially to tumor development in this mouse model of intestinal neoplasia. Our results argue against an oncogenic effect of DNA hypomethylation. Moreover, they are consistent with a role for DNA methyltransferase in the generation of the C to T transitions seen at high frequency in human colorectal tumors.

引用

页码：197 / 205

页数：9

共 74 条

[21] HYPOMETHYLATION OF DNA FROM BENIGN AND MALIGNANT HUMAN-COLON NEOPLASMS [J].