CancerQuest >> Cancer Genes >> Tumor Suppressors

Tumor Suppressors: APC Introduction

Mutations of the APC (adenomatous polyposis coli) gene are strongly associated with both inherited and sporadic cases of colon cancer. As will be described on the next page, the APC protein, like many tumor suppressors, functions to control the expression of genes critical in the cell division process.

Most cases of colon cancer are thought to develop slowly over a period of several years. Inactivation of the APC gene, located on chromosome 5, is thought to lead to increased cell proliferation and contribute to the formation of colonic polyps. Several genetic alterations must occur during the conversion of normal colon cells into cells capable of forming tumors. In many cases mutation of the APC gene is thought to be one of the first steps. Evidence for this can be seen indirectly by examining individuals who have inherited a mutation in one of their APC genes. These patients have a disease called familial adenomatous polyposis, a condition in which the colon is filled with polyps. Every polyp has the potential to develop into cancer, therefore those with the inherited mutation are at a much higher risk for cancer. This situation is very similar to the one described for the inherited form of retinoblastoma in the section devoted to Rb. Instead of needing two somatic mutations within the same cell to lose APC function, these individuals require only a single genetic change.

Comparisons of mutations identified in cells removed at different stages of cancer development have lead to the establishment of a possible order for genetic mutations that lead to a subset of colon cancers. In this model, the APC gene is mutated in the first step, producing highly proliferative cells. Those cells will then form a polyp, which may develop into cancer.