The Role of TGF-beta Signaling in Suppression of Stat3-mediated Tumorigenesis

胃癌是西方世界第三大流行癌症，仅在澳大利亚每年就有数千人死亡。我们发现了一种叫做gp 130的受体分子的特殊基因突变，这种突变导致了小鼠胃癌的形成。我们现在的目标是了解这种突变导致胃采矿细胞不受控制的生长的确切分子事件。我们的建议结合了两位研究人员在信号转导和转基因小鼠模型制作方面的专业知识。这些策略将用于在实验室小鼠中专门解决两个特定信号级联的功能，称为Stat 3和TGF-β。这些分子与癌症形成因果关系的详细描述的鉴定将为未来治疗各种癌症（包括胃癌）的疗法提供明确和特异性的分子靶点。

Stomach cancer is the third most prevalent cancer in the Western World and result in the yearly death of several thousand people in Australia alone. We have discovered a specifice gene mutation of a receptor molecule called gp130 that results in the formation of stomach cancer in mice. We are now aiming to understand the exact molecular events by which this mutation results in the uncontrolled growth of stomach mining cells. Our proposal combines the expertise of the two investigators in signal transduction and the making of genetically modified mouse models. These strategies will be employed to specifically address in the laboratory mouse the function of two specififc signaling cascades, called Stat3 and TGF-beta. The identification of detailed description by which these molecules causally relate to cancer formation will provide clear and specific molecular targets for future therapies to treat various cancers, including those of the stomach.