Author: Wong, Tsz Kwan
Title: Role of catalytic PI3K isoform p110δ on the expression of COL6A1 and macrophage migration inhibitory factor in human glioblastoma
Advisors: To, Tony (HTI)
Degree: M.Sc.
Year: 2016
Subject: Glioblastoma multiforme
Protein kinases.
Phosphoinositides.
Hong Kong Polytechnic University -- Dissertations
Department: Department of Health Technology and Informatics
Pages: xvi , 83 pages : color illustrations
Language: English
Abstract: Glioblastoma multiforme (GBM) is a malignant type of primary brain tumor which is the most aggressive one. The World Health Organization (WHO) classified GBM as grade IV central nervous tumor and yet, it is still incurable. This kind of brain tumor is characterized by high cell proliferation, excessive vascularity, necrosis and chemoresistance. GBM involves a number of mutations and according to the pilot study of our group, deregulation of the signaling of PI3K pathway is the most essential driver in gliomagenesis. The class IA catalytic isoform p110δ is highly expressed consistently in different glioma cell lines and after knockdown of p110δ by small interfering RNA (siRNA), the ability of cell migration and invasion decreased. DNA array of siRNA treated glioma cell lines shown consistently decreased expression of COL6A1. To follow up, we need to first verify the expression of COL6A1 in siRNA treated glioma cell lines and then try to investigate the next target under COL6A1 (i.e. the macrophage migration inhibitory factor (MIF)) which might be involved in glioma cell migration, invasion and proliferation. In this study, we investigated the COL6A1 and MIF expression induced by the p110δ isoform of class IA PI3K. Experiments were performed by knocking down the PIK3CD gene in the U87, U373 and SK-MG3 cell lines using small interfering RNA comparing with the control. Proteins extracted from these cells were detected with Western blot analysis. Our results suggested that expression of COL6A1 and MIF are not affected by the level of p110δ. Results may provide more information on the role of p110δ involved in GBM progression and provide hope to develop new specific drugs against suitable targets against GBM by understanding every members involved in the signaling pathway.
Rights: All rights reserved
Access: restricted access

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