Carcinogenesis cellular model for identifying preventive agents

用于识别预防剂的致癌细胞模型

• 批准号: 7501372
• 负责人: Hwa-Chain Robert Wang
• 金额: $ 7.15万
• 依托单位: UNIVERSITY OF TENNESSEE KNOXVILLE
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-27 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7501372
• 关键词: 4-(Methylnitrosamino)-1-(3-Pyridyl)-1-Butanone; Address; Benzo(a)pyrene; Biological; Biological Markers; Breast; Cancerous; Carcinogen exposure; Carcinogens; Cell Line; Cell model; Cells; Chronic; Collecting Cell; Dependence; Development; Diet; Disease; Dose; Effectiveness; End Point; Environmental Carcinogens; Environmental Pollution; Epithelial; Epithelial Cells; Exposure to; Foundations; Gene Chips; Gene Expression; Gene Expression Regulation; Genes; Goals; Growth Factor; Health; Healthcare; Human; Individual; Knowledge; MCF10A cells; Malignant Neoplasms; Metabolic; Methods; Molecular; Molecular Profiling; Play; Positioning Attribute; Premalignant; Prevention; Preventive; Property; Reagent; Recipe; Research; Risk; Role; Smoker; Societies; Staging; System; Technology; Testing; Tobacco; Work; cancer prevention; cancer risk; carcinogenesis; cell growth; chemical carcinogen; chemical carcinogenesis; cost; cytotoxic; dietary constituent; dietary supplements; experience; exposed human population; fruits and vegetables; malignant breast neoplasm; metaplastic cell transformation; prevent; success; tobacco exposure

Summary The ultimate goal of this project is to further develop an efficient cellular model and methods to identify dietary agents for preventing human cancers induced by tobacco and environmental carcinogens. Studies have suggested that exposures to tobacco and environmental carcinogens increase the risk of cancer development in humans. Growing evidence suggests vegetables and fruits can play a protective role in human healthcare by preventing cancers and other diseases. However, there is a serious gap in our understanding of how dietary constituents prevent human cancers associated with chemical carcinogens. The rationale for this project is to establish a low-cost cellular model and methods to study cellular and molecular mechanisms for dietary agents in the prevention of cellular carcinogenesis induced by tobacco and environmental carcinogens. Using cell technology, we have been developing a carcinogenesis-cellular model mimicking chronic exposures of human breast epithelial cells to low doses (levels detected in smokers) of carcinogens. We have been able to induce cells to progressively acquire cancerous properties, from an immortalized non-cancerous stage through identifiable precancerous sub-stages to a cancerous stage. With gene chip technology, our cellular model serves as a system to reveal the molecular markers of carcinogens in the progressive transformation of human epithelial cells. The central hypothesis is that the identifiable, acquired cancerous properties and molecular markers of cellular carcinogenesis are able to serve as biological and molecular endpoints for the prevention of breast cell carcinogenesis, which will then allow us to determine biological and molecular activities of preventive agents for protecting human cells from carcinogenesis. To test this hypothesis, we will address the capability of our carcinogenesis-cellular model to reveal the ability, the mode of action, and the molecular markers associated with dietary suppression of cell acquisition of cancerous properties induced by individual carcinogens. Success of this study will empirically validate our approach of identifying preventive agents to block carcinogenesis associated with tobacco and environmental pollution, and create a foundation for studying the molecular mechanisms involved in the dietary prevention of carcinogen-related cancers. The broad impact is expected to benefit the whole of society by providing an efficient cellular model to identify dietary constituents for formulating diets or supplements that can prevent human cancers related to tobacco exposure and environmental pollution. Narrative Success of this study will empirically validate our approach of identifying preventive agents to block carcinogenesis associated with tobacco and environmental pollution, and create a foundation for studying the molecular mechanisms involved in the dietary prevention of carcinogen-related cancers. The broad impact is expected to benefit the whole of society by providing an efficient cellular model to identify dietary constituents for formulating diets or supplements that can prevent human cancers related to tobacco exposure and environmental pollution.

概括 该项目的最终目标是进一步开发有效的细胞模型和方法 确定预防由烟草和环境诱发的人类癌症的膳食制剂 致癌物质。研究表明，接触烟草和环境致癌物 增加人类患癌症的风险。越来越多的证据表明蔬菜和水果 可以通过预防癌症和其他疾病对人类保健起到保护作用。然而， 我们对饮食成分如何预防人类癌症的理解存在严重差距 与化学致癌物质有关。该项目的基本原理是建立一个低成本的蜂窝网络 研究膳食制剂预防疾病的细胞和分子机制的模型和方法 烟草和环境致癌物诱发的细胞癌变。利用细胞技术，我们 一直在开发一种模仿人类乳房长期暴露的致癌细胞模型 上皮细胞对低剂量（吸烟者中检测到的水平）致癌物的影响。我们已经能够诱导 细胞逐渐获得癌性特性，从永生化的非癌性阶段到 可识别的癌前亚阶段到癌阶段。借助基因芯片技术，我们的细胞 模型作为一个系统来揭示渐进性致癌物的分子标记 人类上皮细胞的转化。中心假设是可识别的、获得的 癌症特性和细胞癌变的分子标志物能够作为生物 以及预防乳腺细胞癌变的分子终点，这将使我们能够 确定预防剂的生物和分子活性，以保护人体细胞免受 致癌作用。为了检验这个假设，我们将讨论我们的致癌细胞的能力 模型揭示与饮食相关的能力、作用方式和分子标记 抑制细胞获得由个体致癌物诱导的癌特性。 这项研究的成功将从经验上验证我们识别预防药物的方法 阻止与烟草和环境污染相关的致癌作用，并为 研究通过饮食预防致癌物相关癌症的分子机制。 通过提供有效的细胞模型，预计其广泛的影响将使整个社会受益。 确定膳食成分，以制定可以预防人类癌症相关的饮食或补充剂 烟草暴露和环境污染。叙述 这项研究的成功将从经验上验证我们识别预防药物的方法 阻止与烟草和环境污染相关的致癌作用，并为 研究通过饮食预防致癌物相关癌症的分子机制。 通过提供有效的细胞模型，预计其广泛的影响将使整个社会受益。 确定膳食成分，用于配制可预防人类癌症相关的饮食或补充剂 烟草暴露和环境污染。

项目成果

Mesenchymal and stem-like cell properties targeted in suppression of chronically-induced breast cell carcinogenesis.

间充质和干细胞样细胞特性旨在抑制长期诱导的乳腺细胞癌变。

• 发表时间: 2013-06-01
• 影响因子: 9.7
• 作者: Rathore, Kusum;Wang, Hwa
• 通讯作者: Wang, Hwa

Green tea catechin intervention of reactive oxygen species-mediated ERK pathway activation and chronically induced breast cell carcinogenesis.

绿茶儿茶素干预活性氧介导的 ERK 通路激活和长期诱导的乳腺细胞癌变。

• 发表时间: 2012-01
• 影响因子: 4.7
• 作者: Rathore, Kusum;Choudhary, Shambhunath;Odoi, Agricola;Wang, Hwa
• 通讯作者: Wang, Hwa

Grape seed proanthocyanidin suppression of breast cell carcinogenesis induced by chronic exposure to combined 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and benzo[a]pyrene.

葡萄籽原花青素可抑制长期接触 4-(甲基亚硝基氨基)-1-(3-吡啶基)-1-丁酮和苯并[a]芘联合诱导的乳腺细胞癌变。

• 发表时间: 2010-05
• 影响因子: 4.6
• 作者: Song, Xiaoyu;Siriwardhana, Nalin;Rathore, Kusum;Lin, Degui;Wang, Hwa
• 通讯作者: Wang, Hwa