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An Introduction to Tumor Suppressors

Oncogenes: Myc

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CancerQuest > Introduction to Cancer Biology > Cancer Genes > An Introduction to Tumor Suppressors > Tumor Suppressors: APC Function

Tumor Suppressors: APC Function

Since an absence of functional APC protein leads to increased cell division, it stands to reason that the normal protein works to inhibit cell division in some way. This is indeed the case. APC protein forms a complex with beta-catenin, a transcription factor, leading to beta-catenin's degradation. In the absence of the APC protein, there is an excess of beta-catenin in the nucleus. Beta-catenin binds to another protein in the nucleus to form a complex that binds to DNA and activates the transcription of several genes. One target gene of this complex is c-myc, a known oncogene.⁽¹⁾ C-myc is itself a transcription factor for several genes that control cell growth and division. The mutation of the APC gene leads, therefore, to a cascade of events that ultimately result in increased cell division. A diagram of this model of APC function is shown below.

Of course, many other factors can influence the expression of genes and their products, but mutations in the APC genes seem to correlate with an increase in beta-catenin and c-myc leading to high proliferation rates.⁽²⁾

Research has shown that the addition of normal APC protein to colon cancer cells lacking functional APC causes a decrease in tumor cell growth. The decrease in growth was shown to be caused by an increase in apoptosis, suggesting that APC mediates cell death controls as well as growth controls.⁽³⁾ Therefore, loss of the gene alters the balance between cell growth and cell death that acts to control cell numbers.

References for this page:

1. Iwamoto M, Ahnen DJ, Maltzman F, Maltzman T. "Expression of beta-catenin and Full Length APC Protein in Normal and Neoplastic Colonic Tissues." Carcinogenesis (2000). 21(11): 1935-1940. [PUBMED]
2. Fultz KE, Gerner EW. "APC-Dependent Regulation of Ornithine Decarboxylase in Human Colon Tumor Cells." Molecular Carcinogenesis (2002). 34:10-18. [PUBMED]
3. Morin PJ, Vogelstein B, Kinzler KW. "Apoptosis and APC in Colorectal Tumorigenesis." Proc. Natl. Acad. Sci. USA (1996). 93: 7950-7954. [PUBMED]