APC mutation and the crypt cycle in murine and human intestine

Am J Pathol. 1997 Mar;150(3):833-9.

Abstract

Dysplastic colon adenomas are thought to arise from growth of clones of APC -/- colonic epithelial cells. Isolated clusters of dysplastic crypts are often observed in patients with familial adenomatous polyposis. These patients have genotype APC +/-, and the clusters of dysplastic crypts (called microadenoma or aberrant crypt foci) are thought to represent an early stage in the expansion of a mutant clone of APC -/- cells. It is thought that the growth of these clusters of mutant crypts results from crypt replication through a process similar to what occurs in the normal crypt cycle. We measured the relative replication rate of mutant crypts by analyzing the size of clusters of mutant crypts in APC +/- individuals and found that mutant APC -/- crypts replicate more rapidly than do normal APC +/- (i.e., nonneoplastic) crypts. In contrast, the replication rate of mutant crypts in Apc +/- mice is not significantly different from that of normal crypts, thus supporting previous findings that aberrant crypt foci do not contribute significantly to the colon adenoma population in adult Apc +/- mice. Intriguingly, we found an effect of Apc heterozygosity on the frequency of branching crypts in young mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenomatous Polyposis Coli / genetics*
  • Adenomatous Polyposis Coli / pathology
  • Aging / pathology
  • Animals
  • Colon / growth & development*
  • Colon / pathology
  • Colonic Diseases / genetics
  • Colonic Diseases / pathology
  • Colonic Neoplasms / genetics*
  • Colonic Neoplasms / pathology
  • Female
  • Genes, APC / genetics*
  • Humans
  • Jejunum / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mutation*
  • Precancerous Conditions / genetics*
  • Precancerous Conditions / pathology
  • Species Specificity