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SUPPRESSION OF INTESTINAL NEOPLASIA BY DNA HYPOMETHYLATION
Author(s): LAIRD PW, JACKSONGRUSBY L, FAZELI A, DICKINSON SL, JUNG WE, LI E, WEINBERG RA, JAENISCH R
Source: CELL    Volume: 81    Issue: 2    Pages: 197-205    Published: APR 21 1995  
Times Cited: 467     References: 74     
Abstract: 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.
Document Type: Article
Language: English
Reprint Address: LAIRD, PW (reprint author), MIT, WHITEHEAD INST BIOMED RES, CAMBRIDGE, MA 02142 USA
Addresses:
1. MIT, DEPT BIOL, CAMBRIDGE, MA 02142 USA
2. MASSACHUSETTS GEN HOSP E, CARDIOVASC RES CTR, BOSTON, MA 02129 USA
Publisher: CELL PRESS, 50 CHURCH ST CIRCULATION DEPT, CAMBRIDGE, MA 02138
Subject Category: Biochemistry & Molecular Biology; Cell Biology
IDS Number: QV410
ISSN: 0092-8674
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