Mechanisms of oncogenesis and anti-oncogenesis

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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