Adenomatous polyposis coli

Abbreviations LDL, low density lipoprotein TNF-a, tumor necrosis factor-a IL-6, interleukin-6 APC, adenomatous polyposis coli tumor suppressor. 

Adenomatous polyposis coli (APC) gene A tumor suppressor gene, acting as a gatekeeper to prevent development of tumors. A familial cancer syndrome called FAP, or familial adenomatous polyposis, is caused by mutations in APC. Mutation of APC also occurs commonly in sporadic cases of colorectal carcinoma. 

Jorde LB, Watkins WS, Carlson M, Groden J, Albertsen H, Thliveris A, et al. Hnkage disequilibrium predicts physical distance in the adenomatous polyposis coli region. Am J Hum Genet 1994 54 884-898. 

Minowa T et al. Proteomic analysis of the small intestine and colon epithelia of adenomatous polyposis coli gene-mutant mice by two-dimensional gel electrophoresis. Electrophoresis 2000 21 1782—1786. 

Liu, J., et al., Siah-1 mediates a novel beta-catenin degradation pathway linking p53 to the adenomatous polyposis coli protein. Mol Cell, 2001, 7f5 , 927-36. 

Individuals at risk for developing a genetic disease with a delayed age of onset may wish to learn whether they have inherited a disease-causing mutation (e.g., Huntington disease, femilial breast cancer, hemochromatosis, adenomatous polyposis coli). In some cases, presymptomatic diagnosis can be highly usefiil in preventing serious disease consequences before they occur (e.g., phlebotomy for hemochromatosis, early tumor detection for familial breast cancer). 

Miyaki M, Konishi M, Kikuchi-Yanoshita R, et al. Characteristics of somatic mutation of the adenomatous polyposis coli gene in colorectal tumors. Cancer Res 1994 54 3011-3020. 

Since this promoter can be induced by the addition of zinc, it allows for the conditional expression of genes. This induction is especially important if the expression of a particular gene is deleterious to the cell. For example, the adenomatous polyposis coli (APC) tumor suppressor gene was inserted into a vector downstream of the MT II promoter (Morin et al., 1996). Since continuous expression of APC is inhibitory to cell growth, an inducible expression system was necessary to examine the effects of APC expression on cells. This promoter was specifically chosen due to its low basal activity in the absence of zinc The drawbacks to this system are the potential effects that increased zinc concentrations may have in the cell. These effects may include toxicity to the cell or altered gene expression due simply to the presence of zinc. 

Orbit/MAST proteins, also known as CLIP-associated proteins (CLASPs), are involved in the regulation of microtubule dynamics and bind to microtubule plus ends via CLIP115 or CLIP170. Active CLASP suppresses microtubule assembly and axon outgrowth (Lee et al., 2004), whereas activated adenomatous polyposis coli protein (APC see below) promotes microtubule assembly and axon outgrowth. 

The link between Cox-2 and polyps has been most extensively studied in an animal model of FAP, the adenomatous polyposis coli gene knockout mouse, which develops multiple intestinal polyps. In this model, both sulindac and a Cox-2 inhibitor are effective in producing regression of adenomas. When this knockout mouse was crossbred to a Cox-2 knockout mouse to produce a double adenomatous polyposis coli/Cox-2 knockout, the development of intestinal polyposis was markedly reduced (Oshima etal., 1996). 

The adenomatous polyposis coli tumour suppressor gene... 

Normally, cell proliferation and cell death are in a steady state, where the rate of proliferation is matched by the rate of apoptosis. Colon cancer, like other cancers, is caused by mutations in key components of regulatory pathways in this case mutations of the tumour-suppressor gene APC, the adenomatous polyposis coli gene. When APC is inactivated and turned off, the Wnt pathway, normally operative only in the embryo, is turned on. The Wnt pathway also plays a role in other cancers, for example in mammary tumours in mice and humans (for further information and literature references, see ref. 14). 

S. Miinemitsu, I. Albert, B. Souza, B. Rubinfeld, and P. Polakis. Regulation of intracellular beta-catenin levels by the adenomatous polyposis coli (APC) tumor-suppressor protein. Proc Natl Acad Set, USA, 92 (7), 3046-3050, 1995. 

APC, antigen-presenting cells are bone-marrow-derived cells, macrophages and dendritic cells which process foreign antigens and present them to T cells, OR, adenomatous polyposis coli protein, enoded by the human ape gene. 

APC antigen-presenting cell OR anaphase-promoting complex OR adenomatous polyposis coli... 

PolakLs, F- (1997). The adenomatous polyposis coli (AFC) tumor suppressor, Biochim. Bio-phifs. Acta 1332, F127-F147. 

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