Gene-Environment Interactions in Lung Cancer

肺癌中基因与环境的相互作用

• 批准号: 9556629
• 负责人: Brid Ryan
• 金额: $ 38.63万
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9556629
• 关键词: Alzheimer' s Disease; Brain; Bronchi; Catecholamines; Data; Dopamine; Dopamine Agonists; Dopamine Receptor; Epidemiology; Family; Horns; Human; Link; Lung; Malignant Neoplasms; Malignant neoplasm of lung; Metabolism; Molecular; Monograph; Parkinson Disease; Pathway interactions; Patients; Pattern; Play; Publishing; Respiration; Risk; Role; Schizophrenia; Seminal; Signal Transduction; Smoking; Structure of parenchyma of lung; Therapeutic Agents; Tumor Suppressor Proteins; carcinogenesis; follow-up; gene environment interaction; nervous system disorder; receptor

While dopamine signaling and its receptors are well characterized in the brain, there is a paucity of data regarding the role and the expression pattern of dopamine and its receptors in the normal lung. Previous studies have shown that dopamine plays an important role in bronchi-dilation and respiration, however a comprehensive analysis of dopamine, its receptors, transporters and metabolism has not been conducted. We are therefore mapping the dopamine axis in both normal lung tissue and human lung cancer. Our initial studies suggest that certain subtypes of the dopamine receptor family may function as tumor suppressors and we are currently validating those observations and investigating the molecular mechanism. In addition, we are examining the efficacy of specific dopamine receptor agonists and antagonists as therapeutic agents against cancer and analyzing the key mechanistic pathways involved.

虽然多巴胺信号传导及其受体在大脑中得到了很好的表征，但有关多巴胺及其受体在正常肺部中的作用和表达模式的数据却很少。既往研究表明多巴胺在支气管扩张和呼吸中发挥重要作用，但尚未对多巴胺及其受体、转运蛋白和代谢进行全面分析。因此，我们正在绘制正常肺组织和人类肺癌中的多巴胺轴。我们的初步研究表明，多巴胺受体家族的某些亚型可能起到肿瘤抑制因子的作用，我们目前正在验证这些观察结果并研究其分子机制。此外，我们正在研究特定多巴胺受体激动剂和拮抗剂作为癌症治疗药物的功效，并分析所涉及的关键机制途径。