Utilizing TWIST promoter-driven reporter gene as epithelial mesenchymal transition sensor and anti-cancer drug screening platform

• Main Authors: Yi-Jhen Ou, 歐依甄
• Other Authors: Ren-Shyan Liu
• Format: Others
• Language: zh-TW
• Published: 2017
• Online Access: http://ndltd.ncl.edu.tw/handle/72628138663795168209

碩士 === 國立陽明大學 === 生物醫學影像暨放射科學系 === 105 === Tumor is a highly heterogeneous tissue, tumor cells with the ability to self-renewal and rapid abnormal proliferation and differentiation , epithelial mesenchymal transition occurred in the primary tumor and contribute to tumor heterogeneity and promote cancer stem cell characteristics. Epithelial-mesenchymal transitions (EMT) are vital for morphogenesis during embryonic development and wound healing, and also a key mechanistic basis for the progression of malignant tumors. EMT contributes to the establishment of cancer-initiating cells (CIC) in malignant tumors. In order to combat the therapeutic resistance and recurrence caused by this group of cancer-initiating cell , we must use the EMT gene as a predictor to target these EMT-derived cells. Develop a a novel and effective treatment targeted to eliminate these cancer- initiating cell population produced by the epithelial-mesenchymal transformation. According to the study, we know that tumor microenvironment, whether through the inflammatory factors (TNF-α), transforming growth factor (TGF-β), hepatocyte growth factor (HGF), fibroblast growth factor (bFGF) ,Epithelial growth factor (EGF), or HIF1α, HMGA2 can induce the occurrence of epithelial mesenchymal transition, and further upregulation TWIST transcription factor expression . Therefore, we selected EMT key regulator TWIST transcription factor as our molecular marker to detect the possible epithelial-mesenchymal transformation cells in tumor. First, we used the SAS cell line in head and neck squamous cell carcinomas (HNSCC) to establish a stable transfected cell line, SAS-pTwist-E2-Crimson-P2A :: ttksr39, which is driven from Twist promoter to link the dual fusion reporter gene [pTwist- E2-Crimson :: ttksr39] to characterize the EMT-derived cell. Overall, using these repoter system will allow us for tracking EMT-derived cell in real-time and further demonstrate the great potential of multimodality molecular images as a anti-cancer drug screening platform on malignant tumor tracking both in vivo and in vitro, this result can be helpful for future studies of malignancy, targeted therapy, metastasis, and recurrence. Key words: Epithelial-mesenchymal transitions(EMT) 、cancer-initiating cells (CIC)、TWIST