Differential gene expression profiles in colon epithelium of two rat strains with distinct susceptibility to colon carcinogenesis after exposure to PhIP in combination with dietary high fat

Abstract

Colon cancers develop through accumulation of multiple genetic and epigenetic alterations in colon epithelial cells, and the environment of the genetically altered epithelial cells may also have a substantial impact on their further development to cancer. In the present study, groups of 6-week-old F344 and ACI male rats, the former strain being susceptible to colon carcinogenesis induced by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and the latter being relatively resistant, were subjected to a longterm carcinogenesis experiment using our intermittent feeding protocol of PhIP in combination with a high-fat diet, which serves as a relevant risk factor that promotes the development of colon cancers. Animals were sacrificed at 60 weeks, and global gene expression analyses of normal parts of colon epithelial tissues were conducted using a high-density oligonucleotide microarray to elucidate the differential gene expression profile ( umerous studies have indicated that multiple genetic and epigenetic events are involved in the development of colon cancers. Dysregulation of the adenomatous polyposis coli (Apc), β-catenin, p53 and K-ras genes by either genetic alteration or promoter inactivation by CpG methylation plays a key role in colon carcinogenesis.

Microarray Analyses of Genes Differentially Expressed by Diet (Black Beans and Soy Flour) during Azoxymethane-Induced Colon Carcinogenesis in Rats

“…Another cluster of genes influenced by AOM treatment involved moderate induction of several ribosomal proteins. RNA and protein synthesis decrease as cells terminally differentiate [51], and enhanced presence of ribosomal protein transcripts is consistent with findings from other studies in the colon of rats susceptible to PhIP-induced colon cancer [52] and in animals during aging [53]. …”

Gene expression in colorectal neoplasia: modifications induced by tissue ischaemic time and tissue handling protocol

“…RNA‐based studies are particularly important as they reflect the expression of specific genes and, by implication, the ability to generate proteins that support cellular biochemical functions. Assessment of gene expression profiles within diseased tissue therefore enables a genome‐wide screen to identify molecular genetic events that are important in the development of cancer 2–13 . These molecular events determine the properties of the tumour cells that define their biological behaviour, resistance to therapy and, ultimately, prognosis.…”

“…Assessment of gene expression profiles within diseased tissue therefore enables a genome-wide screen to identify molecular genetic events that are important in the development of cancer. [2][3][4][5][6][7][8][9][10][11][12][13] These molecular events determine the properties of the tumour cells that define their biological behaviour, resistance to therapy and, ultimately, prognosis. The level of expression of individual genes that determine these features may be investigated at the mRNA level or at the level of protein expression.…”

The Response of Human Colonocytes to Folate Deficiency in Vitro: Functional and Proteomic Analyses

“…41 Decreased COMT activity is associated with human colorectal cancer recurrence, 44 while elevated COMT gene expression reduces colon tumors in rats. 45 Human SSADH deficiency, a rare genetic defect, impairs CNS gamma-aminobutyrate (GABA) degradation, and is associated with neurological disorders and learning difficulties. To the best of our knowledge, this is the first study to report an association between SSADH expression and folate status.…”