Haploinsufficiency of Flap endonuclease (Fen1) leads to rapid tumor progression Academic Article uri icon

Overview

MeSH Major

  • Adenocarcinoma
  • Endodeoxyribonucleases
  • Intestinal Neoplasms
  • Mutation

abstract

  • Flap endonuclease (Fen1) is required for DNA replication and repair, and defects in the gene encoding Fen1 cause increased accumulation of mutations and genome rearrangements. Because mutations in some genes involved in these processes cause cancer predisposition, we investigated the possibility that Fen1 may function in tumorigenesis of the gastrointestinal tract. Using gene knockout approaches, we introduced a null mutation into murine Fen1. Mice homozygous for the Fen1 mutation were not obtained, suggesting absence of Fen1 expression leads to embryonic lethality. Most Fen1 heterozygous animals appear normal. However, when combined with a mutation in the adenomatous polyposis coli (Apc) gene, double heterozygous animals have increased numbers of adenocarcinomas and decreased survival. The tumors from these mice show microsatellite instability. Because one copy of the Fen1 gene remained intact in tumors, Fen1 haploinsufficiency appears to lead to rapid progression of cancer.

publication date

  • July 23, 2002

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC126601

Digital Object Identifier (DOI)

  • 10.1073/pnas.152321699

PubMed ID

  • 12119409

Additional Document Info

start page

  • 9924

end page

  • 9

volume

  • 99

number

  • 15