| Budget Amount *help |
¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2003: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 2002: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Research Abstract |
The detachment and the release of cancer cells from the original site are thought to be a mimicry of mesoderm differentiation during normal development. Eomesodermin (Eomes) plays a key role in mesoderm differentiation in early development. We examined the expression of Eomes in eight human colon cancer cell lines (SW48, DLD-1, HT29, HCT116, LoVo, SW620, SW480, SW837) by RT-PCR, and found that five (DLD-1, HCT116, LoVo, SW620, SW480) of these colon cancer cell lines unusually expressed Eomes. Eomes expressing cells showed more fibroblastic morphology and more migratory phenotype than Eomes unexpressing cells. Therefore, the expression of Eomes seemed to correlate malignant phenotypes of these colon cancer cells. When examined by RT-PCR, Slug (SnaH/Snail2), other mesoderm differentiation regulator, was also expressed in four (HCT116, LoVo, SW620, SW480) of five colon cancer cell lines expressing Eomes. To examine the role of Eomes in colon cancer progression and the relationship between Eomes and Slug, we cloned human Eomes cDNA from Eomes expressing human colon cancer cells (SW480) and introduced Eomes expression vector into the SW48 cells which expressed neither Eomes nor Slug. Eomes induced the expression of Slug and partially repressed the expression of E-cadherin. When Eomes were introduced into HT29 cells, which were also negative for Eomes and Slug expression, the level of intercellular E-cadherin decreased and cells showed ~more fibroblastic morphology. Since Slug have been reported to suppress the E-acadherin expression in colon cancer cells, Eomes seemed to repressed E-cadherin expression through the function of Slug. Although we had attempted to isolate transfectants stably expressing exogeous Eomes in order to examine the influence of Eomes expression on the migratory phenotype and in vivo malignancy, unfortunately we could not obtain such a stable transfectant.
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