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| SUPPRESSION OF INTESTINAL NEOPLASIA BY DNA HYPOMETHYLATION |
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| 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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