Multistep carcinogenesis of the colon in Apc(Min/+) mouse

Abstract

Colon cancer arises through different histological stages representing different genetic and epigenetic alterations. The Apc(Min/+) mouse has a point mutation at the Apc gene, and it is considered to be a model for human familial adenomatous polyposis. Our previous studies have revealed the presence of a number of intramucosal microadenomas in the colons of Apc(Min/+) mice, in which only a few macroscopic tumors were recognized. These observations suggest that there are two distinct stages for colon carcinogenesis in Apc(Min/+) mouse, and the Apc(Min/+) mouse is regarded as a good model to study multistage colon carcinogenesis. A number of genes that modify intestinal tumorigenesis have been identified using Apc mutant mice combined with other mutant mice. It has become apparent that epigenetic modification strongly affects intestinal tumorigenesis in Apc(Min/+) mice. We herein describe the different stages of colon tumorigenesis and their modifiers, and discuss the possible application of Apc mutant mice in order to better understand the molecular mechanisms of multistage carcinogenesis in the large bowel of humans.

Figure 1

Intestinal tumorigenesis in Apc ^Min/+ mice. A previous study indicated that the process of tumorigenesis in the small intestine is different from that in the colon. There are two histologically distinguishable lesions in the colon of the Apc ^Min/+ mouse.

Figure 2

A model for multistage colon carcinogenesis in mice and its possible modifiers. Genetically engineered mice have shown a number of modifiers for different stages of colon carcinogenesis.