Author: Mok, Siu-fai
Title: Analysis of Phosphoinositide 3-kinase delta (PI3Kδ) expression in glioblastoma multiforme (GBM) from formalin-fixed and paraffin-embedded tissues
Degree: M.Sc.
Year: 2012
Subject: Glioblastoma multiforme.
Protein kinases.
Hong Kong Polytechnic University -- Dissertations
Department: Department of Health Technology and Informatics
Pages: xiii, 85 leaves : ill. (some col.) ; 30 cm.
Language: English
Abstract: Glioblastoma multiforme (GBM) is the most common and most aggressive type of primary brain tumor in humans. GBM is one of the worst prognoses of brain tumor and median survival is 12 months. Epidermal growth factor receptor (EGFR), phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and Phosphoinositide 3-kinase (PI3K) are closely related in cell signaling. EGFR overexpression and PTEN inactivation are often found in glioblastoma. EGFR overexpression increases the PI3K activity, while PTEN inactivation decreases its inhibitory effect on PI3K. Therefore, PI3K activity increases and promotes the downstream cell signaling pathways which in turn facilitates the survival, transformation and cytoskeletal rearrangement of the malignant cells. It has been shown that there is an increase in PI3Kδ isoform expression in GBM cell lines. Therefore, PI3Kδ may play a role in gliomagenesis. Moreover, PI3Kδ is an important component for axonal elongation and regeneration. It is also involved in cell migration, and its role in glioma cell invasion has been reported in vitro. To determine if PI3Kδ is also expressed in GBM in vivo, we used immunohistochemistry and real-time PCR to determine its protein and mRNA levels respectively. The expression of PI3Kδ protein was significantly increased in GBM than in normal brain tissues and pilocytic astrocytoma (P<0.05). A significant correlation with moderate relationship was also found in PI3Kδ protein expression among the tumor grading of astrocytoma (r=0.519; P<0.0001). We also examined the expression level of PI3Kδ mRNA. For the mRNA expression levels, no correlation was found among the tumour grading of astrocytoma (r=0.086, P =0.393) and between the PI3Kδ protein expression (r=0.028; P=0.749). This may be due to the RNA being partially degraded in the formalin-fixed paraffin embedded samples and/or in the process of manual microdissection. Further studies are needed to explore the mechanism of PI3Kδ and its downstream effectors in the PI3K/Akt pathway.
Rights: All rights reserved
Access: restricted access

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