Gene-Environment Interactions in Lung Cancer

我们确定了DRD1和二手烟之间的基因环境相互作用与肺癌风险的关系——这一观察结果在曾经和从不吸烟者中都有发现。虽然多巴胺信号及其受体在大脑中有很好的特征，但关于多巴胺及其受体在正常肺中的作用和表达模式的数据缺乏。以往的研究表明，多巴胺在支气管扩张和呼吸中起重要作用，但尚未对多巴胺及其受体、转运体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具有肿瘤抑制作用，我们目前正在验证这些观察结果并研究其分子机制。此外，我们正在研究特异性多巴胺受体激动剂和拮抗剂作为癌症治疗剂的疗效，并分析所涉及的关键机制途径。

We identified a gene environment interaction between DRD1 and secondhand smoke in relation to lung cancer risk--an observation that was seen in ever and never smokers. 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.