| Summary: | 碩士 === 中山醫學大學 === 醫學研究所 === 98 === Abstract
Constitutive activation of the canonical Wnt signaling pathway is observed in a majority of colon cancers. Daxx reduces activation of the Wnt signaling. Reduction of Daxx protein expression has been observed in colon adenocarcinoma tissue compared with normal colon tissue. Daxx may play an important role in carcinogenesis of colon cancer. The tumor suppressor gene P53 plays signicant roles in growth arrest, DNA repair and apoptosis, by acting as a transcription factor to modulate the expression of various genes. Recently researchs have suggest that Daxx interacts with P53. In this present study, we want to examine effect of Daxx on the P53-mediated tumor suppression in colorectal cancer. In Daxx knock down stable cells, decreasing of Daxx resulted in P53 reduction, and transient transfection with Daxx could rescue this reduction. Following Proliferation rate assay was measured to demonstrat Daxx knockdown cell significantly increase growth rate compared with control vector transfected cells, Daxx and P53 overexpresssion can retard the growth rate of Daxx knock down cells. These results show that Daxx can upregulation expression of P53 in CRC cells. Hct116 cells were treated with UV irradiation for 30min,Etoposide (ETO), 5-fluorouracil (5-FU), Mitomycin C (MMC) for 24 and 48hr to induced P53 and apoptosis. Downregulation of Daxx by shRNA strongly potentiated P53-dependent apoptosis in HCT116. With clinical 130 paired colon adenocarcinoma tissues were comparison in protein detection by western blotting. The evidences indicated the decreased Daxx accompany P53 reduction in almost halt of paired tissues(55％,72 /130).These results may indicate that reduction of Daxx can repress P53 expressing in CRC, and Daxx silencing sensitizes Hct116 cells to DNA damage induced apoptosis , Daxx may be a potential novel target for future anticancer therapeutic development in colon cancer.
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