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Effect of selenium-enriched broccoli diet on differential gene expression in min mouse liver(1,2)
Huawei Zeng1, Cindy D Davis, John W Finley
1United States Department of Agriculture, Grand Forks Human Nutrition Research Center, Grand Forks, North Dakota 58202-9034, USA. hzeng@gfhnrc.ars.usda.gov
Abstract:
Multiple intestinal neoplasia (Min) mice are a good model for investigating the effects of dietary alterations in a genetic model for intestinal cancer. Previous studies have shown that selenium-enriched broccoli effectively reduces colon cancer susceptibility. Although colon cancer cells mainly metastasize to the liver, little is known about the effects of selenium-enriched broccoli on gene expression in mouse liver. To better understand the protective role for selenium-enriched broccoli in tumorigenesis, a gene profile of the mouse liver was analyzed. Mice were fed either 0.11 mg selenium/kg control diet or 2.1 mg selenium/kg selenobroccoli diets for 10 weeks. Use of mouse pathway finder-1 GEArrays revealed that selenium-enriched broccoli moderately increased ikBalphakappaB, hsp86, gadd45 gene transcripts. In addition, analysis of the binding of liver nuclear proteins to (32)P-labeled probes demonstrated that selenium-enriched broccoli enhanced the binding of transcription factor p53, NFkappaB, AP-1 to their cis-acting elements. Collectively, these results suggest for the first time that selenium-enriched broccoli activates certain pro-apoptotic genes linked to p53, NFkappaB and stress signal pathways in response to "danger signals" such as tumorigenesis.
Insights
Selenium-enriched broccoli activates cancer-fighting pathways in mouse liver. This study reveals how this dietary intervention impacts gene expression, offering insights into colon cancer prevention.
Area of Science:
- * Nutritional immunology
- * Molecular oncology
- * Cancer prevention
Background:
- * Multiple intestinal neoplasia (Min) mice serve as a valuable genetic model for studying intestinal cancer.
- * Selenium-enriched broccoli has demonstrated efficacy in reducing colon cancer susceptibility.
- * The impact of selenium-enriched broccoli on gene expression in mouse liver, a common site for colon cancer metastasis, remains largely unexplored.
Purpose of the Study:
- * To investigate the effects of selenium-enriched broccoli on gene expression in the liver of Min mice.
- * To elucidate the molecular mechanisms underlying the protective role of selenium-enriched broccoli in tumorigenesis.
Main Methods:
- * Min mice were fed either a control diet or a selenium-enriched broccoli diet for 10 weeks.
- * Gene expression profiling was performed using mouse pathway finder-1 GEArrays.
- * Analysis of transcription factor binding to DNA was conducted using labeled probes.
Main Results:
- * Selenium-enriched broccoli consumption led to a moderate increase in the gene transcripts ikBalphakappaB, hsp86, and gadd45.
- * Enhanced binding of transcription factors p53, NFkappaB, and AP-1 to their cis-acting elements was observed in the liver.
- * These findings suggest activation of stress signal pathways and pro-apoptotic genes.
Conclusions:
- * Selenium-enriched broccoli activates specific pro-apoptotic genes associated with p53, NFkappaB, and stress signaling pathways.
- * This activation occurs in response to tumorigenesis-related "danger signals".
- * The study provides novel insights into the molecular mechanisms of selenium-enriched broccoli in cancer prevention.