Paper Summary:

This paper is an examination of the mechanisms of colon tumorigenesis involving the mutation cluster region of the APC gene. There is an explanation of colon carcinogenesis including an analysis of the Wnt signaling pathway, the roles of the APC gene's different domains, "Knudon's two- hit hypothesis and the "just right" level of signaling theory. The paper also includes a critical discussion about the scientific arguments and research evidence that exists to challenge current understanding of the underlying mechanisms of colon tumorigenesis. One illustration is included which depicts the varying domains of the APC gene.

From the Paper:

"Colorectal cancer is the third most common form of cancer and the second leading cause of death in the western world. Nearly 34,900 people are diagnosed with it in the U.K each year and about 16,000 of these die. About 15% of colorectal cancers are hereditary. Hereditary conditions are divided into two categories: the polyposis and the non polyposis types. Two hereditary conditions that have been identified are Familial Adenomatous Polyposis Coli (FAP) and Hereditary Non Polyposis Colorectal Cancer (HNPCC). The adenomatous polyposis coli (APC) gene is known to be mutated in all cases of FAP but this condition only accounts for less than 1% of colorectal cancer cases. The condition HNPCC results when mutation occurs in the DNA mismatch repair genes MSH2 and MLH-1 leading to microsatellite instability and defective DNA repair. Non inherited mutations of the APC gene have been detected in over 85% of the remaining sporadic colorectal cancers. "

Sample of Sources Used:

• Kufe, Pollack,Weich et al. (2003). Cancer Medicine, Sixth Edition, BC Decker Inc, Hamilton.
• Mahdevaiyer, S. Xu,C., Gumbiner, B.M. (2006). Characterization of a 60S complex of the adenomatous polyposis coli: tumour suppressor protein. Biochica et Biophysica Acta 1773:120-130
• Hanson,C and Miller, J. (2005). Non-traditional roles for the adenomatous polyposis coli (APC) tumor suppressor protein. Gene 361:1-12
• Mimori-Kiyosue,Y. Shiina, N. Tsukita, S. (2000).The dynamic behaviour of the APC-binding protein EB1 on the distal ends of microtubules. Current Biology 10:865-868
• Nakamura, M. Zhou, X. Lu, K. (2001). Critical role for the EB1 and APC interaction in the regulation of microtubule polymerization. Current Biology 11:1062-1067

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