P53 Biomaker and Intervention in Occupational Cancer

P53 Biomaker 与职业癌症干预

基本信息

批准号：
6753496
负责人：
Paul W Brandt-Rauf
金额：
$ 20.93万
依托单位：
COLUMBIA UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2002
资助国家：
美国
起止时间：
2002-06-01 至 2006-05-31
项目状态：
已结题

项目摘要

DESCRIPTION: Research Methods for Occupational Cancer are needed to develop early markers of adverse health effects from workplace exposures and to devise ways for interrupting the pathways between workplace exposures and resultant cancers. The p53 tumor suppressor gene product is a potential target for both of these approaches. Certain occupational exposures can produce mutations in p53 which cause the generation of an immune response with circulating p53 auto-antibodies, even before the occurrence of clinically detectable cancers, so that these antibodies may serve as useful early markers of adverse effects. In addition, certain short peptide sequences from p53 have been demonstrated in cell culture to be able to cause mutant p53 to revert to normal function, resulting in the death of cancer cells containing mutant p53 but with no effect on normal cells with wild-type p53, suggesting that this may be a useful approach for interrupting the pathway between workplace exposures that produce p53 mutations and resultant cancers. The purpose of the proposed research is to examine both of these approaches for occupational cancers caused by asbestos exposure in two related projects. For the first project, banked serum samples from a cohort of workers with asbestosis will be examined for the presence of p53 auto-antibodies by enzyme-linked immunosorbent assay and ininiunoblotting to determine if the presence of the antibodies correlates with the subsequent development of cancer, as well as with the presence of p53 mutations in the resultant tumors. For the second project, the effects in cell culture of a p53 peptide sequence (delivered as the peptide or as a plasmid-based mini-gene) on asbestos-associated lung cancer and mesothelioma cell lines with and without p53 mutations and corresponding non-cancer cell lines with wild-type p53 will be investigated, as well as determining the mechanism of action of the peptide for inducing death in these cells.

描述：需要开发职业癌症的研究方法工作场所接触不良健康影响的早期标志并制定中断工作场所暴露与由此产生的影响之间的途径的方法癌症。 p53 肿瘤抑制基因产物是两者的潜在靶点这些方法。某些职业接触可能会产生突变 p53 引起循环 p53 产生免疫反应自身抗体，甚至在临床可检测到的癌症发生之前，因此这些抗体可以作为不良反应的有用早期标记。此外，p53 的某些短肽序列已在细胞培养能够使突变的p53恢复正常功能，导致含有突变 p53 的癌细胞死亡，但没有效果在具有野生型 p53 的正常细胞上，表明这可能是有用的中断工作场所暴露之间途径的方法 p53 突变和由此产生的癌症。拟议研究的目的是检查这两种方法治疗石棉引起的职业癌症参与两个相关项目。对于第一个项目，储存血清样本将检查一组患有石棉沉着病的工人是否存在通过酶联免疫吸附测定和免疫印迹法检测 p53 自身抗体以确定抗体的存在是否与随后的相关癌症的发展，以及 p53 突变的存在由此产生的肿瘤。对于第二个项目，p53 对细胞培养的影响肽序列（作为肽或基于质粒的小基因传递）石棉相关肺癌和间皮瘤细胞系有或没有 p53 突变和相应的具有野生型 p53 的非癌细胞系进行研究，并确定肽的作用机制用于诱导这些细胞死亡。