Role of phosphoinositide 3-kinase delta (PI3K[delta]) in glioblastoma cell lines

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Role of phosphoinositide 3-kinase delta (PI3K[delta]) in glioblastoma cell lines


Author: Ng, Kwok-hong Peter
Title: Role of phosphoinositide 3-kinase delta (PI3K[delta]) in glioblastoma cell lines
Degree: M.Sc.
Year: 2006
Subject: Hong Kong Polytechnic University -- Dissertations.
Glioblastoma multiforme.
Department: Dept. of Health Technology and Informatics
Pages: xi, 90 leaves : ill. (some col.) ; 30 cm.
Language: English
Abstract: PI3K is an important family of enzymes involved in cell signaling. The PI3K/Akt pathway is overexpressed in many cancers including glioblastoma multiforme. Since PI3K8 isoforms have unique features and are expressed in glioblastoma cell lines, they are attractive targets for studying their roles and their downstream effectors. This study investigated, one of the PI3K isoforms, the catalytic subunit p1108 and its downstream effectors including p-Akt and p-p44/42MAPK in 3 different glioblastoma cell lines. Other isoforms and downstream effectors such as p110a, p110b, Akt and MAPK were also being investigated so that more meaningful data could be collected. The expression of p110a, p110b, Akt and MAPK were similar among the U343, U87 and GBM6840 cell lines. On the other hand, the expression of p1108 was found inversely proportional to p-Akt. Mutation on PIK3R1 gene encoding the p85 subunit might have accounted for this observation, in fact, a mutation had been reported in the exon 12-13 junction of PIK3R1 gene of a glioblastoma multiforme patient. However, no mutation was identified at both of these exons in this study. Based on the wortmannin treatment and expression of p-Akt and p-p44/42MAPK analysis, certain signaling characteristics of the selected cell lines can be deduced. The GBM6840 cell line does not favour both the PI3K/Akt and Ras/MAPK pathway. However, the GBM6840 has high p1108 expression. How the p1108 subunit involved in cell signaling in this cell line is still questionable. Although this study cannot conclude the entire role of PI3K8 in glioblastoma multiforme, it provides significant information for further studies.

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