| Budget Amount *help |
¥21,970,000 (Direct Cost: ¥16,900,000、Indirect Cost: ¥5,070,000)
Fiscal Year 2013: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2012: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2011: ¥9,230,000 (Direct Cost: ¥7,100,000、Indirect Cost: ¥2,130,000)
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| Research Abstract |
This study aimed to clarify the roles of pleckstrin homology domain containing, family G member 1 (PLEKHG1) gene encoding a member of Dbl-family RhoGEFs, in development and progression of colon cancer. Knockdown of PLEKHG1 in HCT 116 colon cancer cells resulted in increased proliferation rate and decreased cell-cell adhesion in vitro. The Plekhg1 gene knockout in Apc mutant mice, a model for familial adenomatous polyposis (FAP) and the early stage of colon cancer development, resulted in increased number of colonic polyps in the large size class. On the other hand, induction of epithelial-mesenchymal transition (EMT) in colon cancer cells led to a dramatic increase in the PLEKHG1 mRNA level, and forced expression of PLEKHG1 in colon cancer cells resulted in enhanced invasion activity through Matrigel. These results suggest that although PLEKHG may have a tumor suppressor-like function in early stage of colon cancer formation, it may promote invasion at later stages.
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