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The roles of cell cycle and BRCA1 in the DNA damage response
* 1 , 2 , 3 , 4 , 5 , 1 , 6 , 7
1  Division of Risk Assessment, Center for Biological Safety and Research, National Institute of Health Sciences
2  Innovation Centre of NanoMedicine (iCONM), Kawasaki Institute of Industrial Promotion
3  Division of Cellular and Molecular Toxicology, Center for Biological Safety and Research, National Institute of Health Sciences
4  Department of Bioengineering, Graduate School of Engineering, The University of Tokyo
5  Department of Clinical Genomics, National Cancer Center Research Institute
6  Department of Pathology, Kobe University of Graduate School of Medicine
7  Department of Translational Oncology, National Cancer Center Research Institute


Molecular network activation states alter dynamically in biology and diseases. In cancer stem cells (CSCs), epithelial-mesenchymal transition (EMT) networks play an important role to acquisition of the drug resistance and cancer malignant feature. To reveal the network pathways in EMT and CSCs, gene expression in diffuse- and intestinal-type gastric cancer (GC) have been analyzed. The several canonical pathways have been found to be altered in diffuse- and intestinal-type GC. Canonical pathway on Cell Cycle: G1/S Checkpoint Regulation was activated in diffuse-type GC, and Cyclins and Cell Cycle Regulation was activated in intestinal-type GC. In Cell Cycle: G1/S Checkpoint Regulation, DNA damage induces p53, which was predicted to be activated in diffuse-type GC. Canonical pathway related to Role of BRCA1 in DNA Damage Response was activated in intestinal-type GC, where BRCA1 which is related to G1/S phase transition was up-regulated. Cell cycle regulation may be altered in EMT condition in diffuse-type GC.

Keywords: gastric cancer; cell cycle; epithelial-mesenchymal transition; cancer stem cell