Identification and Characterization of Li-Cadherin in Hepatocellular Carcinoma
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Identification and Characterization of Li-Cadherin in Hepatocellular Carcinoma

Identification and Characterization of Li-Cadherin in Hepatocellular Carcinoma


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This dissertation, "Identification and Characterization of LI-cadherin in Hepatocellular Carcinoma" by Wing-yan, Wong, 王詠恩, was obtained from The University of Hong Kong (Pokfulam, Hong Kong) and is being sold pursuant to Creative Commons: Attribution 3.0 Hong Kong License. The content of this dissertation has not been altered in any way. We have altered the formatting in order to facilitate the ease of printing and reading of the dissertation. All rights not granted by the above license are retained by the author. Abstract: Abstract of thesis entitled Identification and Characterization of LI-cadherin in Hepatocellular Carcinoma submitted by WONG Wing-Yan for the degree of Master of Philosophy at The University of Hong Kong in August 2003 Liver-intestine cadherin (LI-cadherin) is a transmembrane glycoprotein mediating ++ Ca -dependent homophilic cell-cell adhesion. It locates at gene locus 8q22.1 where genomic instability is frequently found in hepatocellular carcinoma (HCC). Unlike classical cadherin, the extracellular domain consists of seven cadherin-type repeats and the cytoplasmic tail is short with only 20 amino acids. Previous studies demonstrated that LI-cadherin was expressed in developmental stage of rat liver and intestine. However, its expression was not found in adult liver and normal gastric mucosa. During intestinal metaplasia transition, LI-cadherin expression is induced. Further evidence showed strong expression of LI-cadherin in well-differentiated ductal adenocarcinoma of the pancreas. Except these two pieces of findings, limited evidences have provided clues for its role in other cancers. Locating at the hot spot of genetically gain in expression in HCC, LI-cadherin gene may be important in hepatocarcinogenesis. To gain an initial insight on the role of LI-cadherin in HCC, the aim of this study is to investigate LI-cadherin gene ii and protein expression in HCC cell lines and tissues and compared with non-tumorous counterpart. RT-PCR analysis showed that three tumorigenic HCC cell lines, Hep3B, HuH-7, and PLC/PRF/5, but not the MIHA (normal fetal liver) nor HepG2 (non-tumorigenic) expressed mRNA of LI-cadherin. The expression of LI-cadherin gene in cell lines was further confirmed by TaqMan real-time quantitative RT-PCR. As revealed by immunofluorescence staining, immunostaining for LI-cadherin localized predominantly in the cytoplasm of the HCC cells. In contrast, classical cadherins that mainly distributed on the cell-cell contact site. Further examination of clinical specimens by immunohistochemical analysis showed that LI-cadherin expressed in 21 out of 39 (53.85%) HCC cases. Over-expression of LI-cadherin was significantly correlated with cirrhosis in non-tumor liver (P = 0.023). Interestingly, LI-cadherin staining was found in different cellular compartments of tumor cells. Accumulations of staining in nuclear, cytoplasm and/or cytoplasmic membrane were observed. Patients showing cytoplasmic and membranous LI-cadherin protein in tumors had significantly shorter overall survival than those without the expression (P = 0.0435, P=0.0285 respectively). iii In addition, preliminary analysis by Western blot described a truncated variant of LI-cadherin with 90 kDa in 14/16 (87.5%) of HCC tissues. Sequencing analysis of shorten gene product showed alternative splicing of exon 7 in LI-cadherin gene in HCC samples. In conclusion, it is demonstrated for the first time expression of LI-cadherin in HCC cell lines and tissues. Expression of LI-cadherin in tumorigenic HCC but not in non-tumorigenic and normal liver cells suggested that it may be useful as a new marker molecule to differentiate between normal cells and tumorigenic HCC cells. Over-expression of LI-cadherin in HCC suggested that it may play an important role in hepatocarcinogenesis. A more detailed understanding of relationship between subcellular LI-cadherin ex


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Product Details
  • ISBN-13: 9781374713826
  • Publisher: Open Dissertation Press
  • Publisher Imprint: Open Dissertation Press
  • Height: 279 mm
  • No of Pages: 108
  • Weight: 268 gr
  • ISBN-10: 1374713821
  • Publisher Date: 27 Jan 2017
  • Binding: Paperback
  • Language: English
  • Spine Width: 6 mm
  • Width: 216 mm


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