Suppression of intestinal neoplasia by deletion of Dnmt3b Academic Article uri icon

Overview

MeSH Major

  • DNA (Cytosine-5-)-Methyltransferase
  • Gene Deletion
  • Gene Expression Regulation, Neoplastic
  • Gene Silencing
  • Intestinal Neoplasms

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.

publication date

  • April 2006

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC1446955

Digital Object Identifier (DOI)

  • 10.1128/MCB.26.8.2976-2983.2006

PubMed ID

  • 16581773

Additional Document Info

start page

  • 2976

end page

  • 83

volume

  • 26

number

  • 8