Mechanisms of oncogenesis and anti-oncogenesis

这一优先领域科学研究补助金的目的是阐明肿瘤发生和抗癌发生的机制。一方面，为了阐明肿瘤发生的分子机制，我们设置了三个类别的分析，包括分子和细胞（A01），器官和个体（A02）和群体（A03）水平。我们已经探索了1）基因和染色体结构稳定的分子机制，2）基因组结构中稳态维持的机制，3）内源性和外源性因素对这种稳态的破坏与细胞中肿瘤发生表型之间的关系，4）新的癌症相关基因，5）分子，通过器官和个体中癌症相关基因的积累的多步骤致癌的细胞和生物学机制，以及6）通过基于家族和群体的研究的分析的癌症相关基因。另一方面，为了阐明分子防御机制， ...更多信息 在肿瘤发生中，我们设置了两类分析，包括内源性稳态维持机制（A04）和免疫系统（A05）。我们从细胞色素P450、错配修复基因等维持体内平衡的机制和免疫系统对癌细胞的排斥机制等方面探讨了抗肿瘤的分子机制。特别是在DNA修复机制的破坏与肿瘤发生的关系的阐明、H. pyroli在胃癌中的作用，3）阐明Wnt-、Shh-和PI 3 K-Akt信号通路在体内肿瘤发生中的关键作用，4）鉴定21号染色体上的胃癌易感基因，5）鉴定上皮癌中的许多肿瘤抗原，6）NK和辅助T细胞在抗肿瘤发生中的作用，和7）先天免疫系统在适应性免疫中的作用，基于这些发现，我们正在进一步发展癌症治疗的转化研究。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