Suppression of Intestinal Neoplasia by Deletion of Dnmt3b.
From: Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02141, USA.
Molecular and cellular biology
- Publish Date: Apr 2006
- ISSN: 0270-7306
- Volume: 26
- Issue: 8
- Pages: 2976-83
- Medium: Print
- Language: English
- Citation (JAMA): Lin Haijiang, Yamada Yasuhiro, Nguyen Suzanne, et al. Suppression of Intestinal Neoplasia by Deletion of Dnmt3b.. Mol. Cell. Biol. Apr 2006;26:2976-83
Abstract
Aberrant gene silencing accompanied by DNA methylation is associated with neoplastic progression in many tumors that also show global loss of DNA methylation. Using conditional inactivation of de novo methyltransferase Dnmt3b in Apc(Min/+) mice, we demonstrate that the loss of Dnmt3b has no impact on microadenoma formation, which is considered the earliest stage of intestinal tumor formation. Nevertheless, we observed a significant decrease in the formation of macroscopic colonic adenomas. Interestingly, many large adenomas showed regions with Dnmt3b inactivation, indicating that Dnmt3b is required for initial outgrowth of macroscopic adenomas but is not required for their maintenance. These results support a role for Dnmt3b in the transition stage between microadenoma formation and macroscopic colonic tumor growth and further suggest that Dnmt3b, and by extension de novo methylation, is not required for maintaining tumor growth after this transition stage has occurred.
Mesh Headings (Keywords): Adenoma, Alleles, Animals, Blotting, Western, DNA (Cytosine-5-)-Methyltransferase, DNA Methylation, DNA, Neoplasm, Gene Deletion, Gene Expression Regulation, Neoplastic, Gene Silencing, Immunohistochemistry, Intestinal Neoplasms, Mice, Mice, Inbred C57BL, Mice, Knockout, Models, Biological
Check for Full Text / PubMed Unique Identifier (PMID): 16581773
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