Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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Outline of Final Research Achievements |
Esophagogastric junction, like cervix of uterus, is composed of squamous and columnar cells, and known to be highly carcinogenic. However, the cause and mechanism of esophogogastric cancer is largely unsolved. In this study, we have examined the origin and mechanism of mouse gastric squamocolumnar junction (SCJ) tumor. KRAS and TGFbR2 mutation in KRT19+ cells led to invasive tumor specifically at gastric SCJ. This tumor showed columnar cell marker KRT7, squamous cell marker KRT14, and several stem cell markers, such as SOX9 and CD44. Organoid culture of SCJ tumor cells revealed these tumors can survive and grow independently of Wnt, EGF, or Noggin stimulation. In normal mouse, KRT19+ cells are observed in the deep lesion of gastric gland especially at SCJ, showing stem cell property in the lineage tracing experiment. In contrast, Lgr5+ cells did not make SCJ tumor upon KRAS and TGFbR2 mutation, suggesting KRT19+, Lgr5- SCJ gland cells can be the origin of SCJ tumor in our model.
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