Proteomic Signatures of Cancer

环境物质似乎与乳腺癌的病因学有关。几项研究已经 发现人类癌症与接触农业杀虫剂之间的联系，如 有机氯(OC)农药；因此，农场工人可能面临更高的急性和慢性健康风险 与杀虫剂相关的影响。该项目目标有两个：1)获得流行病学数据 具体到农药使用率高和低的地区的乳腺癌发病率，以及2)暴露在正常乳房 在培养上皮细胞中加入有机氯化合物，以确定其生物学效应。这是对 中央山谷拉美裔农场工人的健康差距。对于第一阶段，学生研究人员将计算 使用杀虫剂的年龄调整的乳腺癌发病率，并从哪些其他变量中确定数据库 与乳腺癌流行病学相关的知识是有用的。在有希望的结果之后，个别乳腺癌病例 (和健康的“对照”)将被接洽并被招募进入#年的乳腺癌病例对照研究 其中收集了基于问卷的信息和生物标本。DNA将被提取出来 从唾液中提取并在弗雷斯诺州用PCR技术对几种常见的致癌代谢物进行基因分型 基因。在第二阶段，学生研究人员将测试有机氯对 来自NCI/合作社西班牙裔参与者的原代正常人类乳腺上皮细胞 人体组织网络。在长期OC处理下维持的细胞将通过蛋白质组学进行比较 第一年用2D-PAGE和LC-MS/MS进行表达谱分析，第二年用基因表达谱分析。 最后，将与BIMR化学基因组核心一起对OC耐药细胞进行筛选 雌激素效应的逆转。这一创新的试点项目将带领学生了解一系列癌症 从识别高危人群到对问题的分子分析等方面的研究。

Environmental substances seem to be involved in the etiology of breast cancers. Several studies have found an association between human cancer and exposure to agricultural pesticides such as the organochlorine (OC) pesticides; therefore, farmworkers may be at higher risk for acute and chronic health effects associated with pesticides. The objective of this project is two-fold, 1) obtain epidemiological data specific to breast cancer incidence rates in areas of high and low pesticide use, and 2) expose normal breast epithelial in culture with organochlorine chemicals to determine the biological effects. This is responsive to the health disparity of Hispanic farmworkers in the Central Valley. For Phase 1, student researchers will calculate age-adjusted breast cancer incidence rates for pesticide use and identify databases from which other variables pertinent to breast cancer epidemiology are useful. Upon promising results, individual breast cancer cases (and healthy "controls") will be approached and recruited for entry into a breast cancer case-control study in which both questionnaire-based information and biological specimens are collected. DNA will be extracted from saliva and genotyped by PCR techniques at Fresno State for several of the common carcinogenmetabolizing genes. For Phase 2, student researchers will test the biological effects of organochlorines on primary normal human mammary epithelial cells derived from Hispanic participants of the NCI/Cooperative Human Tissue Network. Cells maintained under long-term OC treatment will be compared by proteomic expression profiling by 2D-PAGE and LC-MS/MS in year 1 followed by gene expression profiling in year 2. Finally, OC-resistant cells will be screened in conjunction with the BIMR Chemical Genomics Core for reversion of the estrogenic effects. This innovative pilot project takes students through a range of cancer research aspects from identifying at-risk populations to molecular analyses of the problem.