GENE EXPRESSION IN DIET INDUCED PROSTATE CANCER

饮食诱发的前列腺癌中的基因表达

• 批准号: 6226333
• 负责人: JAN GELIEBTER
• 金额: $ 15.65万
• 依托单位: NEW YORK MEDICAL COLLEGE
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-02-05 至 2003-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6226333
• 关键词: androgen receptor; animal tissue; apoptosis; arachidonate; cell growth regulation; dietary lipid; eicosanoid metabolism; estrogen receptors; gene expression; immunocytochemistry; male; meat; messenger RNA; microarray technology; neoplasm /cancer genetics; northern blottings; nutrition related neoplasm /cancer; nutrition related tag; prostate neoplasms

Epidemiological studies suggest that a high fat diet for more than one generation is associated with an increased risk of prostate cancer. A more complete understanding of the molecular basis for prostate cancer initiation, promotion and progression by dietary fat is essential for the design of rational programs for prostate cancer prevention and treatment. We have maintained ACI rats on a high beef fat diet (22.52% by weight) for two generations (mothers and male pups) and observed that 2nd-generation male rats develop prostatic neoplasia at a higher incidence, and earlier in life, than rats on a control, 5% fat diet. It is significant that rats on the high beef fat diet developed neoplasia in the dorsal lobes of the prostate, as the dorsal lobe of the rat prostate is homologous to the peripheral zone of the human prostate, where prostate cancer is most prevalent. All animal studies and histological analyses have been completed and we have prepared RNA from dorsal prostates of 6, 12 and 18-month-old 2nd-generation rats. We now propose to analyze the molecular differences in the dorsal prostates of rats maintained on a high fat diet, compared to rats on a control diet to follow gene expression through the progressive molecular stages of diet-induced prostatic neoplasia. We propose to use Affymetrix microarrays (approximately 7000 genes) to identify differences in mRNA expression profiles in the dorsal prostates of rats on high beef fat and control diets. Further we propose to use northern blots and immunohistochemistry to confirm data obtained using microarrays and to identify the cell types differentially expressing the genes in question. The successful completion of these experiments will contribute to our understanding of the molecular basis of diet-associated prostate cancer. Further, it can potentially identify intermediate biomarkers that are modulated by diet and are relevant to human prostate cancer.

流行病学研究表明，一代人以上的高脂肪饮食与前列腺癌风险增加有关。 更全面地了解饮食脂肪对前列腺癌起始、促进和进展的分子基础对于设计合理的前列腺癌预防和治疗方案至关重要。 我们维持ACI大鼠高牛肉脂肪饮食（22.52%重量）的两代（母亲和雄性幼崽），并观察到第二代雄性大鼠前列腺肿瘤的发生率较高，并在生命早期，比对照组，5%脂肪饮食的大鼠。 值得注意的是，高牛肉脂肪饮食的大鼠在前列腺背叶中发生了肿瘤，因为大鼠前列腺的背叶与前列腺癌最普遍的人类前列腺的外周区同源。 所有的动物研究和组织学分析已经完成，我们已经从6，12和18个月大的第二代大鼠的背侧前列腺制备RNA。 我们现在建议分析的分子差异，在背侧前列腺的大鼠保持高脂肪饮食，与对照饮食的大鼠通过饮食诱导的前列腺肿瘤的渐进分子阶段的基因表达。 我们建议使用Affyssin微阵列（约7000个基因），以确定高牛肉脂肪和对照饮食的大鼠背侧前列腺中的mRNA表达谱的差异。 此外，我们建议使用北方印迹和免疫组织化学，以确认使用微阵列获得的数据，并确定差异表达的基因的细胞类型的问题。 这些实验的成功完成将有助于我们理解饮食相关前列腺癌的分子基础。 此外，它可以潜在地识别受饮食调节并且与人类前列腺癌相关的中间生物标志物。