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

胃癌是西方世界第三大最常见的癌症，每年仅在澳大利亚就有数千人死于胃癌。我们已经发现了一种叫做gp130的受体分子的特定基因突变，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生长的确切分子事件。我们的建议结合了两位研究者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处理两个特定的信号级联的功能，称为Stat3和tgf - β。确定这些分子与癌症形成因果关系的详细描述将为未来治疗包括胃癌在内的各种癌症提供明确和特定的分子靶点。

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.