Mechanisms of oncogenesis and anti-oncogenesis

这项优先领域科学研究补助金的目的是阐明肿瘤发生和抗肿瘤形成的机制。一方面，为了阐明肿瘤发生的分子机制，我们建立了三类分析，包括分子和细胞(A01)、器官和个人(A02)和群体(A03)水平。我们从基因和染色体结构稳定的分子机制，基因组结构中维持动态平衡的机制，内源性和外源性因素破坏这种动态平衡与细胞致癌表型的关系，新的癌症相关基因，5)癌症相关基因在器官和个体中积累的多步致癌的分子、细胞和生物学机制，以及6)通过家系和基于人群的研究分析癌症相关基因。另一方面，为了阐明…的分子防御机制在更多的肿瘤发生方面，我们设置了两类分析，包括内源性体内平衡维持机制(A04)和免疫系统(A05)。我们从细胞色素P450和错配修复基因等多种动态平衡维持机制以及免疫系统对癌细胞的排斥机制等方面探讨了抗肿瘤作用的分子机制。特别是，我们在1)阐明DNA修复机制中断与肿瘤发生的关系，2)鉴定胃癌中霍乱弧菌的分子，3)阐明Wnt-、Shh-和PI3K-Akt信号通路在体内肿瘤发生中的关键作用，4)21号染色体上胃癌易感基因的鉴定，5)上皮性癌中多种肿瘤抗原的鉴定，6)NK和辅助T细胞在抗肿瘤发生中的作用，7)天然免疫系统在适应性免疫中的作用，以及在这些发现的基础上，我们正在进一步开展癌症治疗的翻译研究。较少

The aim of this Grant-in-Aid for Scientific Research on Priority Areas was to elucidate the mechanisms of oncogenesis and anti-oncogenesis. On one hand, for the elucidation of molecular mechanisms of oncogenesis, we had set three categories of analyses, including molecular and cellular (A01), organ and individual (A02), and population (A03) levels. We have explored 1) the molecular mechanisms of the stability of structure of genes and chromosomes, 2) mechanisms of maintenance of homeostasis in the genome structure, 3) the relation between disruption of this homeostasis by endogenous and exogenous factors and tumorigenic phenotype in cells, 4) new cancer-related genes, 5) molecular, cellular and biological mechanisms of multistep carcinogenesis through the accumulation of cancer-related genes in organs and individuals, and 6) the cancer-related genes through the analysis by family and population based studies. On the other hand, for the elucidation of the molecular defense mechanisms ag … More ainst oncogenesis, we had set two categories of analyses, including endogenous homeostatic maintenance mechanisms (A04) and immune system (A05). We have explored the molecular mechanisms for anti-oncogensis through the several homeostatic maintenance mechanisms such as CYP450 and mismatch repair genes and exclusion mechanisms of cancer cells by immune system. Especially, we have had remarkable progresses in 1) the elucidation of the relation between disruption of DNA-repair mechanisms and oncogenesis, 2) identification the molecule in H. pyroli in stomach cancer, 3) elucidation of the critical roles of Wnt-, Shh-and PI3K-Akt signaling pathways in oncogenesis in vivo, 4) identification of stomach cancer susceptibility genes on the chromosome 21, 5) identification of many tumor antigens in epithelial cancer, 6) the role of NK and Helper T cells in anti-oncogenesis, and 7) the role of innate immune system in adaptive immunity, and based on these findings we are further developing the translational research for therapy of cancer. Less