Summary: | 碩士 === 長庚大學 === 醫學生物技術研究所 === 93 === In head and neck cancer, pharyngolaryngeal cancer (PLC) is a very critical disease because the anatomy site controls vocal and swelling function. Since pharyngolaryngeal area is rich in lymphatic tissues, PLC has highly invasive and metastatic potential. However, the molecular factor that contributes to PLC invasion is obscure. In this study, using Matrigel and Transwell selection method, we have successfully established four generations of two PLC cell subline cells (FADU and Detroit 562), which provide materials for further screening of potential invasive-associated genes. Two potential invasive-associated genes: 14-3-3-σ and GRP78 were examined in PLC cells. Characterization of the PLC invasive sublines showed a higher migration and invasion abilities, in accompany of down regulation of 14-3-3-σ and up regulation of GRP78. Knock-down 14-3-3-σ expression by RNAi technique increases cell invasion in both FADU and Detroit cells as determined by Matrigel invasion assay. This result suggests 14-3-3-σ negatively regulates PLC cell invasion. Whereas, knock-down GRP78 decreases cell growth, colony formation and cell invasion in both FADU and Detroit cells, suggesting GRP78 positively regulates PLC cell proliferation and invasion. Furthermore, stably knock-down GRP78 significantly inhibits cell invasion and tumor formation in xenograft nude mice. Since suppression of GRP78 significantly inhibits the carcinogenic potential, this molecule may be a potential novel target for molecular adjuvant therapy in PLC.
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