The role of MELK in HCC cell lines

• Main Authors: Yu-Tsun Lin, 林育存
• Other Authors: Ann-Ping Tsou
• Format: Others
• Language: zh-TW
• Published: 2009
• Online Access: http://ndltd.ncl.edu.tw/handle/crbrtm

碩士 === 國立陽明大學 === 醫學生物技術暨檢驗學系暨研究所 === 97 === In eukaryotes, protein kinases catalyze phosphorylation that regulate numerous key physiological functions such as cell proliferation, cell cycle progression, and apoptosis. Hence, aberrantly overexpressed protein kinases are relevant to cancers and many other diseases. Previously, we demonstrated that the mRNA level of MELK, maternal embryonic leucine zipper kinase, is highly elevated in HCC tissues. Knockdown of MELK led to cell apoptosis in HuH7, PLC/PRF5, and Hep3B cells but only moderate growth slowly in HepG2, SK-HEP-1, and Mahlavu cells. We further demonstrated that silencing of MELK suppressed the tumorgenicity of HCC cells both in vitro and in vivo. Thus, MELK is critically involved in liver tumorigenesis. We first studied the protein expression and cellular distribution of MELK in HCC tissues by immunohistochemistry. MELK is localized in the cytoplasm of both normal and HCC tissues. But the protein level in normal tissues is much higher than that in tumor tissues. Since MELK is a cell-cycle regulated protein kinase via cell cycle-mediated degradation, it is highly likely that the MELK protein is rapidly degraded in the proliferating HCC tumor cells but not in the quiescent normal liver tissues. Since silencing of MELK triggered differential responses in different HCC cell lines the roles of MELK substrates are being studied. Based on the bioinformatic prediction, a group of 143 proteins has potential to interact with MELK, of which the expression level of 17 proteins is higher in HCC tissues than in the normal tissues. Understanding the identities and roles of MELK substrates will shed more light on the mechanistic roles of MELK in hepatocarcinogenesis.