Full metadata record
| DC Field | Value | Language |
|---|---|---|
| dc.contributor | Department of Health Technology and Informatics | en_US |
| dc.contributor.advisor | To, Shing-shun Tony (HTI) | - |
| dc.creator | Sin, Chiu Chung | - |
| dc.identifier.uri | https://theses.lib.polyu.edu.hk/handle/200/8370 | - |
| dc.language | English | en_US |
| dc.publisher | Hong Kong Polytechnic University | - |
| dc.rights | All rights reserved | en_US |
| dc.title | Effect of PI3K δ isoform on the expression of integrin beta 3 and p130cas in glioblastoma multiforme | en_US |
| dcterms.abstract | Glioblastoma multiforme (GBM) is a major form of glioma (54%), one of the most aggressive cancers. GBM is an astrocytic, grade IV glioma that presents with the histological features of necrosis and microvascular proliferation. For adults with newly diagnosed GBM, median survival rarely extends beyond 12 months due to poor responses to all therapeutic methods. The current standard treatment is surgery followed by radiotherapy with concomitant chemotherapy using temozolomide. In recent years, cilengitide, an integrin beta3 inhibitor, has been used to treat GBM. PI3Ks are lipid kinases that mediate signaling transduction through receptor tyrosine kinases and G protein-coupled receptors. The main function of PI3K is to regulate cell functions like growth, proliferation, survival, and intracellular trafficking. P110δ, a catalytic subunit of PI3Ks is highly expressed in cancer cell lines, the overexpression of p110δ affect proliferation, and the migration of cancer cells. Integrins are heterodimeric cell surface receptors that bind to the extracellular matrix (ECM). Up to now, at least 24 distinct integrin heterodimers have been formed by combining any of the 18∝ and 8β subunits. Generally, integrins play a role in cell adhesion, regulating cell-cell and cell-ECM interactions. They activate the tyrosine phosphorylation of focal adhesion kinase (FAK), and FAK binds to other signaling structural proteins - PI3K, paxillin, and p130cas. Integrins regulate important signal transduction pathways for cell growth, proliferation, migration, and apoptosis. Aberrant integrin expression will lead to the inhibition of apoptosis, induction of cell proliferation, ECM remodeling, migration, invasion, metastasis, and angiogenesis. These are the elements of cancer progression. Some studies have shown that different integrins are expressed in different tumors. In glioblastoma, integrin beta 3 and integrin beta 5 are expressed at the tumor-normal tissue margin and have a possible role in invasion. Also, the level of expression of integrin beta 3 appears to correlate with the progression of certain cancers, including glioma. P130cas is a downstream molecule of integrin in the signaling pathway, and it acts an integrin adaptor protein. It takes part in cell adhesion, migration, transformation, growth factor stimulation, and cytokine receptor engagement. Overexpression of p130cas has been linked to poor prognosis in many types of cancer. Our previous studies have demonstrated that knocking down PI3K P110δ isoform in GBM cells will decrease their migration and invasion capacity. Using cDNA PCR array analysis, integrin beta 3 (ITGB3) mRNA expression was consistently decreased in 3 different GBM cell lines. Therefore, the aim of this study was to verify the downregulation of integrin beta 3 and p130cas, a downstream target of integrin beta 3, after knocking down the PI3KCD isoform in GBM cell lines U87, U373, and SK-MG3. Our finding is that there was no significant change of ITGB3 and p130cas after the si knockdown procedure. We suggest that more studies be performed to confirm the effect on ITGB3 and p130cas after knockdown of the PI3KCD gene. | en_US |
| dcterms.extent | xiii, 53 pages : color illustrations | en_US |
| dcterms.isPartOf | PolyU Electronic Theses | en_US |
| dcterms.issued | 2016 | en_US |
| dcterms.educationalLevel | All Master | en_US |
| dcterms.educationalLevel | M.Sc. | en_US |
| dcterms.LCSH | Glioblastoma multiforme. | en_US |
| dcterms.LCSH | Phosphoinositides. | en_US |
| dcterms.LCSH | Protein kinases. | en_US |
| dcterms.LCSH | Hong Kong Polytechnic University -- Dissertations | en_US |
| dcterms.accessRights | restricted access | en_US |
Files in This Item:
| File | Description | Size | Format | |
|---|---|---|---|---|
| b28563827.pdf | For All Users (off-campus access for PolyU Staff & Students only) | 3.14 MB | Adobe PDF | View/Open |
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