Characterization of the gene expression network that underlies the progression and coagulopathy of the C6 glioma cells

• Main Authors: Wen Hsin Wu, 吳玟欣
• Other Authors: C. M. Tan
• Format: Others
• Published: 2012
• Online Access: http://ndltd.ncl.edu.tw/handle/57850775490516421568

碩士 === 長庚大學 === 生物醫學研究所 === 100 === Metastasis are the major cause of human cancer deaths. During metastasis, it is of great challenge for cancer cells to survive in the bloodstream, and tumor cell-induced coagulation is necessary. In clinic, up to 50% cancer patients are with thrombotic symptoms. Alteration on transcription programs is one of the important features in tumor cells, and it further results in metastasis. In eukaryotic genomes, transcription factors and their upstream signaling cascades are related to the regulation of gene expression. Dissecting the molecular mechanisms underlying progression will help us to realize how tumor cells become metastatic and correlate with coagulation. In this study, C6 rat glioma cell lines as experimental mode, we have demonstrated differential expression of genes in circulating tumor cells though microarray-based gene expression profiling analysis. However, the regulation mechanisms of diverse gene expressions are not clear. According to metastatic potential and coagulability, we have selected PDPN as target gene to identify its transcriptic regulation and possible pathophysiological significance. Using ChIP assay and online bioinformatic tools, we recently reveal that the presence of epigenetic makers (histone H3/4 acetylation and H3 methylation) and signaling pathway (Akt and BMP7/TGFβ) may participate in gene regulatory expressions of C6 cell lines. Subsequently, after the HDAC inhibitor (TSA) treatment, it is found that the increase of H3K9ac in C6 lung cell is proportional to the level of PDPN expression. However, another metastatic cell line, C6 blood cell line, even with up-regulation of PDPN expression as C6 lung cell line, may exhibit a different mechanism of regulation for this target gene expression. Once the metastatic mechanisms are demonstrated, there is a pivotal and potential clue to cancer therapeutic development.