The effects of exogenous Oct4 and Nanog to cellular behaviors of colorectal cancer cells

• Main Authors: Ming-Long Tsai, 蔡明龍
• Other Authors: Shih-Hwa Chiou
• Format: Others
• Language: zh-TW
• Published: 2011
• Online Access: http://ndltd.ncl.edu.tw/handle/f773r9

碩士 === 國立陽明大學 === 臨床醫學研究所 === 99 === In recent years, increasing incidence and recurrence rate of colorectal cancers have been observed and ages of patience diagnosis with colorectal cancers are decreasing and the mortalities of patience with colorectal cancer are increasing. Besides, colorectal cancer is so far the most prevalence type of cancer in Taiwan. Hypothesis has that cancer may rise from a small population of cancer cells which possess stem cell like properties and these cancer stem-like/initiating cells involves many aspects of tumorigenesis: tumor formation, metastasis, and recurrences. Based on these assumptions, we ask whether it is possible to establish inducible cancer stem-like/initiating cells by transferring two stemness genes: Oct4 and Nanog in SW480 and HT29 which are both colorectal cancer cell lines. We totally established six colorectal cancer cell lines: HT29-pCDH, HT29-Oct4, HT29-Nanog, SW480-pCDH, SW480-Oct4, and SW480-Nanog as model systems for further studies for in vitro cell biological based studies and in vivo animal models for studying tumor growth and metastasis. In vitro experiment results support that overexpression of Oct4 or Nanog promotes cell morphology and overexpressing of Oct4 increases cellular adhesion abilities of colorectal cells, while Nanog overexpression, on the other hand, increases the self-renewal abilities in both SW480 and HT29 cells and furthermore, overexpression of Nanog induces expressions of other stemness genes. Among those cytokines we had examined, overexpression of Oct4 increases the expression levels of IL-8 transcripts in HT29 cells, and Nanog overexpression triggers the expression levels of IL-6, IL-8, and IL-32 transcripts in SW480 cells. However, there is little or no effect of Oct4 overexpression on β-Catenin, MAPK, and PI3K/AKT signaling pathways. Surprisingly, overexpression of Nanog among HT29 and SW480 cells shows completely opposite effects. The animal model experiments have shown that overexpression of Oct4 or Nanong promotes stronger tumorigenicity effects in HT29 cell. Namely, several tumorigenicity properties of HT29 and SW480 cells are increased in overexpression of Oct4 or Nanog, the effects are even more pronounced in in vivo experiments and metastasis. However, the detailed mechanisms downstream of Oct4 and Nanog still need further investigations.