title: The signal pathways in azoxymethane-induced colon cancer and preventive implications.
abstract: Colon cancer is the third most common cancer and third most common cause of cancer-related death in the USA according to 2008 American Cancer Society statistics. The carcinogenesis of colon cancer has been associated with both genetics and environmental factors. It has been found that several signal pathways, including K-ras, Src/PI3K/Akt, beta-catenin, TGFbeta and p53 play critical roles in its pathogenesis. The 5 y survival rate of metastatic colon cancer is below 10%. Thus, it is necessary to further understand its biology and search for effective therapy. Azoxymethane (AOM) is a common model for colon cancer. It can specifically induce colon cancer similar to the pathogenesis of human sporadic colon cancer. Thus, it has been extensively used in the study of the molecular biology, prevention and treatment of colon cancer. After administration, AOM is metabolised into methylazoxymethanol by CYP2E1, which causes DNA mutations. Mutation of K-ras activates this pathway and its downstream PI3K/Akt pathway and MAPK pathway. Mutation of beta-catenin also prevents it from being degraded by GSK-3 and accumulation of beta-catenin leads to cell proliferation. TGFbeta, a pro-apoptotic protein, is inhibited. All of these changes form the basis of AOM carcinogenesis. This model has been used in the study of the genetic deficiencies of colon cancer and in the prevention and treatment of the disease. For example, TGF-betaR2 and adiponectin knockout mice are more susceptible to AOM, while high amylose cornstarch, green tea and artemisia have protective effects.
authors.affiliation: Illawarra Health and Medical Research Institute, University of Wollongong, NSW, Australia. jiezhong@uow.edu.au
authors.forename: Jiezhong
authors.initials: J
authors.lastname: Chen
authors.forename: Xu-Feng
authors.initials: XF
authors.lastname: Huang
mesh_terms: D000230:Adenocarcinoma / Q000139:chemically induced* / Q000503:physiopathology / Q000517:prevention & control; D000236:Adenoma / Q000139:chemically induced* / Q000503:physiopathology / Q000517:prevention & control; D052242:Adiponectin / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis; D001397:Azoxymethane / Q000493:pharmacokinetics / Q000633:toxicity*; D002273:Carcinogens / Q000493:pharmacokinetics / Q000633:toxicity*; D003110:Colonic Neoplasms / Q000139:chemically induced* / Q000503:physiopathology / Q000517:prevention & control; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects; D004032:Diet; D011905:Genes, ras; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008746:Methylazoxymethanol Acetate / Q000031:analogs & derivatives / Q000633:toxicity; D051379:Mice; D018345:Mice, Knockout; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors; D053781:Transforming Growth Factor beta2 / Q000172:deficiency / Q000235:genetics
chemical_list: D052242:Adiponectin; D016588:Anticarcinogenic Agents; D002273:Carcinogens; D016212:Transforming Growth Factor beta; D053781:Transforming Growth Factor beta2; D008746:Methylazoxymethanol Acetate; D019392:Cytochrome P-450 CYP2E1; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; C030667:methylazoxymethanol; D001397:Azoxymethane