Skip to main content
ARS Home » Southeast Area » Little Rock, Arkansas » Microbiome and Metabolism Research Unit » Research » Publications at this Location » Publication #172805

Title: DIETARY EXPOSURE TO SOY OR WHEY PROTEINS ALTERS COLONIC GLOBAL GENE EXPRESSION PROFILES DURING VAT COLON TUMORIGENESIS

Author
item SIMMEN, FRANK - UAMS/ACNC
item BADGER, THOMAS - UAMS/ACNC
item XIAO, RIJIN - ACNC

Submitted to: Molecular Cancer
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/11/2005
Publication Date: 1/11/2005
Citation: Simmen, F.A., Badger, T.M., Xiao, R. 2005. Dietary exposure to soy or whey proteins alters colonic global gene expression profiles during vat colon tumorigenesis. Molecular Cancer. 4(1):1.

Interpretive Summary: We previously showed that lifetime consumption of soy protein or whey protein reduced the incidence of cancers in rat large intestine. To learn how these diets cause this effect, we studied the gene expression profiles of colons from rats fed casein, soy protein isolate, and whey protein hydrolysate. We identified 31 genes that were increased in their expression and 50 genes that were decreased in their expression in colons of soy-fed animals. We also identified 44 genes that were increased and 120 decreased genes in the colons of the whey-fed group. The identification of genes affected similarly by soy and whey suggests common as well as unique anti-cancer mechanisms for each diet. Future studies will investigate the roles of these gene affects in the development in the gastrointestinal tract and in the prevention of GI diseases, especially cancer.

Technical Abstract: Background: We previously showed that lifetime consumption of soy protein or whey protein reduced the incidence of azoxymethane (AOM)-induced tumors in rat colon. The molecular mechanisms underlying the anti-cancer properties of soy and whey are largely unknown. To obtain insights into such mechanisms, global gene expression profiles of colons from rats with lifetime ingestion of casein (CAS, control diet), soy protein isolate (SPI), and whey protein hydrolysate (WPH) diets were determined. Results: Male Sprague Dawley rats, fed one of the three purified diets, were studied at 40 weeks after AOM injection and when tumors had developed in some animals in each group. Total RNA was purified from the proximal half of each colon (non-tumor tissue) and used to prepare biotinylated probes, which were hybridized to Affymetrix RG_U34A rat microarrays containing probes sets for 8799 rat genes. Microarray data were analyzed using DMT (Affymetrix), SAM (Stanford) and pair-wise comparisons. Differentially expressed genes (SPI and/or WPH vs. CAS) were found. We identified 31 induced and 50 repressed genes in the proximal colon of the SPI-fed group and 44 induced and 120 repressed genes in the proximal colon of the WPH-fed group, relative to CAS. Hierarchical clustering identified the co-induction or co-repression of multiple genes by SPI and WPH. The differential expression of I-FABP (2.92-, 3.97-fold down-regulated in SPI and WPH fed rats; P=0.023, P=0.01, respectively), Cyclin D1 (1.61-, 2.42-fold down-regulated in SPI and WPH fed rats; P=0.033, P=0.001, respectively), and the c-neu proto-oncogene (2.46-, 4.10-fold down-regulated in SPI and WPH fed rats; P<0.001, P<0.001, respectively) were confirmed by real-time quantitative RT-PCR. SPI and WPH affected neuro-endocrine gene expression in colon: peptide YY (PYY) and glucagon mRNAs were down-regulated in WPH fed rats, whereas somatostatin mRNA and corresponding circulating protein levels, were enhanced by SPI and WPH. Conclusions: The identification of genes co-regulated by SPI and WPH as well as genes differentially regulated by these diets suggests common as well as unique anti-tumorigenic mechanisms of action. SPI and WPH induction of somatostatin, a known anti-proliferative agent for colon cancer cells, may inhibit tumorigenesis.