Genetic dissection of the gp130 signalling network; implications in the initiation of gastric cancer

gp130信号网络的基因剖析；

• 批准号: nhmrc : 234702
• 负责人: Prof Andrew Giraud
• 金额: $ 29.84万
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2003
• 资助国家: 澳大利亚
• 起止时间: 2003-01-01 至 2005-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/genetic-dissection-gp130-gastric-cancer/97169
• 关键词: Genetic; dissection; gp130; signalling; network

Stomach cancer is a major health problem in the world. It is the second most common cancer and the second leading cause of death from cancer, behind lung cancer. In fact, approximately 10% of all new reported cancer cases world-wide are stomach cancer. The risk of stomach cancer increases with age, with risk rising progressively and peaking at about 60 years of age. Men are affected twice as often as women Like all cancers, stomach cancer results from the progressive acquisition of mutations in genes that normally ensure a balance between cell growth and cell death. Mutations which predispose individuals to stomach cancer accumulate in the epithelial cells that provide the lining to the stomach. The progression of stomach cancer proceeds through a number of distinct anatomical stages which can be easily recognised by pathologists. Mutations in a number of genes (known as Kirsten-ras, p53) are commonly found in stomach tumours. Moreover, some of the mutations are highly associated with distinct stages of tumour development. As yet, however, we have no real insights into how these mutations cooperate with each other to produce full-blown (malignant) stomach cancer. In our proposal, we are aiming to establish stomach cancer in mice. Our approach will be to use an existing animal model which is predisposed to stomach cancer. We will progressively introduce mutant genes into stomach epithelial cells and study how they cooperate with each other to produce benign, and ultimately, malignant tumours in the stomach of mice. This will help us to understand which mutant genes are required for each stage in tumour development and may provide more rational approaches to stomac cancer screening and treatment.

胃癌是世界上一个主要的健康问题。它是仅次于肺癌的第二大常见癌症和第二大癌症死亡原因。事实上，全世界所有新报告的癌症病例中约有10%是胃癌。胃癌的风险随着年龄的增长而增加，风险逐渐上升，并在60岁左右达到顶峰。男性受影响的频率是女性的两倍。与所有癌症一样，胃癌是由基因突变的渐进性获得引起的，这些基因突变通常确保细胞生长和细胞死亡之间的平衡。使个体易患胃癌的突变在提供胃衬里的上皮细胞中积累。胃癌的进展通过许多不同的解剖学阶段进行，这些阶段可以很容易地被病理学家识别。许多基因（称为Kirsten-ras，p53）的突变通常在胃肿瘤中发现。此外，一些突变与肿瘤发展的不同阶段高度相关。然而，到目前为止，我们还没有真实的见解，这些突变如何相互合作，以产生全面的（恶性）胃癌。在我们的提案中，我们的目标是在小鼠中建立胃癌。我们的方法是使用现有的易患胃癌的动物模型。我们将逐步将突变基因引入胃上皮细胞，并研究它们如何相互合作，在小鼠胃中产生良性肿瘤，并最终产生恶性肿瘤。这将有助于我们了解肿瘤发展的每个阶段都需要哪些突变基因，并可能为胃癌的筛查和治疗提供更合理的方法。