Lu Yan, Yao Ruisheng, Yan Ying, Wang Yian, Hara Yukihiko, Lubet Ronald A, You Ming
Department of Surgery and The Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Cancer Res. 2006 Feb 15;66(4):1956-63. doi: 10.1158/0008-5472.CAN-05-3158.
Green tea has been shown to be a potent chemopreventive agent against lung tumorigenesis in animal models. Previously, we found that treatment of A/J mice with either green tea (0.6% in water) or a defined green tea catechin extract (polyphenon E; 2.0 g/kg in diet) inhibited lung tumor tumorigenesis. Here, we described expression profiling of lung tissues derived from these studies to determine the gene expression signature that can predict the exposure and efficacy of green tea in mice. We first profiled global gene expressions in normal lungs versus lung tumors to determine genes which might be associated with the tumorigenic process (TUM genes). Gene expression in control tumors and green tea-treated tumors (either green tea or polyphenon E) were compared to determine those TUM genes whose expression levels in green tea-treated tumors returned to levels seen in normal lungs. We established a 17-gene expression profile specific for exposure to effective doses of either green tea or polyphenon E. This gene expression signature was altered both in normal lungs and lung adenomas when mice were exposed to green tea or polyphenon E. These experiments identified patterns of gene expressions that both offer clues for green tea's potential mechanisms of action and provide a molecular signature specific for green tea exposure.
在动物模型中，绿茶已被证明是一种有效的化学预防剂，可预防肺癌发生。此前，我们发现用绿茶（水中0.6%）或特定的绿茶儿茶素提取物（茶多酚E；饮食中2.0 g/kg）处理A/J小鼠可抑制肺癌发生。在此，我们描述了源自这些研究的肺组织的表达谱分析，以确定能够预测绿茶在小鼠体内的暴露情况和功效的基因表达特征。我们首先分析了正常肺组织与肺肿瘤组织中的整体基因表达，以确定可能与肿瘤发生过程相关的基因（肿瘤相关基因）。比较了对照肿瘤和绿茶处理肿瘤（绿茶或茶多酚E）中的基因表达，以确定那些在绿茶处理肿瘤中表达水平恢复到正常肺组织中所见水平的肿瘤相关基因。我们建立了一个17基因表达谱，该表达谱特定于暴露于有效剂量的绿茶或茶多酚E。当小鼠暴露于绿茶或茶多酚E时，这种基因表达特征在正常肺组织和肺腺瘤中均发生了改变。这些实验确定了基因表达模式，这些模式既为绿茶的潜在作用机制提供了线索，又提供了特定于绿茶暴露的分子特征。
