| Summary: | 碩士 === 國立中興大學 === 生命科學系所 === 100 === Cadherins are a group of cell adhesion proteins that mediate Ca2+-dependent cell-cell adhesion. Meanwhile, cadherins also mediate cell morphology, contact inhibition, and signal transduction during tumorgenesis. There are at least 80 members of the cadherin superfamiliy in mammalians including classic cadherins, desmosomal cadherins, Fat like cadherins, and protocadherins. Protocadherin-19 (PCDH19) is a member of the non-clustered δ2- protocadherin family, which has been shown to be expressed thoughout the central nervous system in mammals. Up to now, many researches reported that protocadherins are involved in the development of the central nervous system, while its regulatory functions in tumor cells of cancer research are poorly understand. Recently, a number of PCDH genes have been implicated as tumor suppressor genes. As tumor-specific promoter methylation is a marker for tumor suppressor genes, and in our previous study we have found that PCDH19 gene is hypermethylaed in hepatocellular carcinomas, therefore we want to investigate the tumor-suppressive function of PCDH19 gene in hepatocellular carcinoma. In this study we used the methylation-specific PCR, COBRA, and bisulfate-sequencing to examine the methylation level of PCDH19 gene in hepatocellular carcinomas, and we found that PCDH19 gene is hypermethylaed in clinical sample of hepatocellular carcinomas. To investigate the functions of PCDH19 expressed in hepatoma cells, PCDH19 gene was overexpressed in Huh7 human hepatoma cell line. In in vitro study, we examined the physiologic effects of PCDH19 on cell proliferation, cell migration and cell invasion of the PCDH19-overexpressed Huh7 cells. The results showed that PCDH19 overexpression would inhibit the proliferation, migration and invasion ability of Huh7 hepatoma cells. We further investigated the expressions of cell cycle related genes and tumorgenesis genes in PCDH19-overexpressed Huh7 cells, and found that PCDH19 might inhibit cell proliferation via p21-induced cell cycle arrest pathway. Our data showed that PCDH19 gene is frequently hypermethylated in hepatocellular carcinomas, and PCDH19 gene might act as a tumor-suppressive function in hepatoma cell line.
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