| Author: | Or, Mei-li |
| Title: | Genes involved in cell migration signaling pathways induced by the p110δ isoform of class IA phosphoinositide 3-kinase in glioblastoma multiforme |
| Degree: | M.Sc. |
| Year: | 2011 |
| Subject: | Glioblastoma multiforme. Gliomas. Phosphoinositides. Hong Kong Polytechnic University -- Dissertations |
| Department: | Department of Health Technology and Informatics |
| Pages: | xiii, 107 leaves : ill. (some col.) ; 30 cm. |
| Language: | English |
| Abstract: | Glioblastoma multiforme (GBM) is the most aggressive malignant brain tumor in humans with poor prognosis because of its active migration action and resistance to apoptosis. Recent clinical and experimental data have shown that increased cell migration, cell motility and resistance to apoptosis are results of changes at the genomic, transcriptional and post-transcriptional level of proteins, protein kinases and their transcriptional factor effectors. The PTEN/PI3K/Akt/mTOR, and the Ras/Raf/MEK/ERK intracellular signaling pathways play critical roles in the regulation of gene expression and prevention of apoptosis in GBM. The aberrant activity of the PI3K pathway and its isoforms has been specifically reported to correlate with adverse clinical outcomes in human GBM. Since glioma cell proliferation and migration are constituent to the severity of this disease, gaining greater insights into the molecular mechanisms regulating these phenotypes is important for improving clinical management in the future. PI3K is a family of dual specificity protein and lipid kinases that regulate a number of intracellular signaling pathways involved in multiple cellular processes. Various studies have established a link of the p110δ isoform of with carcinogenesis. There are increasingly more reports on the expression of the p110δ isoform in tumors. Moreover, it has been shown to be involved in regulating glioma cell migration and cell motility. In this study, we investigated the potential oncogenic transformation induced in the extracellular matrix and adhesion pathways by the p110δ isoform of class IA PI3K. Experiments were performed by knock down the PIK3CD gene in the U87 cells by RNA interference technique comparing with the control. Reverse-transcribed cDNA from these cells were applied to two 96 well Extracellular Matrix and Adhesion Molecules PCR array plates respectively. The plates were containing genes that are relevant to cell migration and invasion. The plates were run in the 7500 Real-Time PCR System. Then all the results of their cycle threshold values were collected and analyzed through the DataAssist™ software. Finally, the fold change value was calculated to determine the up- or down-regulation of genes. Our results suggested that five most outstanding genes, namely, ITGB3, ITGA5, ITGA7, TGFBI and TIMP1 may be directly affected by the p110δ isoform. The changes in their expression correlate with the changes in the ECM that may lead to inhibition of glioma cell proliferation, migration and angiogenesis via different biological pathways. |
| Rights: | All rights reserved |
| Access: | restricted access |
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| File | Description | Size | Format | |
|---|---|---|---|---|
| b2458065x.pdf | For All Users (off-campus access for PolyU Staff & Students only) | 2.42 MB | Adobe PDF | View/Open |
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