Author: Lee, Paul
Title: The validation of down regulated genes COL6A1 and THBS3 in p110δ pathogenesis
Degree: M.Sc.
Year: 2014
Subject: Glioblastoma multiforme
Gliomas -- Genetic aspects.
Hong Kong Polytechnic University -- Dissertations
Department: Department of Health Technology and Informatics
Pages: xiv, 69 leaves : illustrations (some color) ; 30 cm
Language: English
Abstract: Giloblastoma multiforme (GBM) is a highly invasive and an aggressive primary brain tumor noticeably the loss of the phosphatase group and the deletion of the homolog tensin in chromosome 10 resulting in the loss of the PTEN function are common features of GBM. The PTEN (Phosphatase and tensin homolog) acts as a very important tumor suppressor by inhibiting the phosphoinositide 3-kinase (PI3K)-Akt signaling pathway through phosphorylating phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) to phosphatidylinositol 3,4,5-triphosphate (PtdIns(3,4,5)P3). Hence, PTEN-PI3K-Akt constitutes an important signaling pathway on the regulation of various cellular responses including cell proliferation, such as the migration / invasion & growth, the metabolism of cellular activity, and also cell apoptosis. The loss of the suppressing functions of PTEN results in the accumulation of phosphatidylinositol 3,4,5-triphosphate leading to the PI3K activation effects, hence it results in the initiation of downstream effectors. The deregulation of the PI3K signaling pathway is considered to be the key pathways in gliomagenesis. In this study, we used small interfering RNAs (siRNA) to selectively inactivate one of the three Class IA PI3K isoforms, p110 delta, to validate and confirm the down-regulation of the two selected genes from a previous PCR array plate study in PTEN-deficient U-373MG glioma cells. Previously, a PCR array plate was initiated and 30 different gene regulations were identified, in which two of the genes COL6A1 and THBS3 have shown a substantial fold change towards down-regulating p110 delta. 7 genes have shown to up-regulate towards p110 delta.
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