|Author:||Lam, Wai Che|
|Title:||Validation of gene expression TGFBI & TIMP1 induced by p110δ isoform of class IA phosphoinositide 3-kinase (PI3K) in glioblastoma multiforme|
Gliomas -- Genetic aspects.
Hong Kong Polytechnic University -- Dissertations
|Department:||Department of Health Technology and Informatics|
|Pages:||xiv, 153 leaves : ill. ; 30 cm.|
|Abstract:||Glioblastoma multiforme (GBM) is the most aggressive and highly invasive Grade IV astrocytoma. Its active migration and apoptosis resistance lead to poor prognosis in GBM. Completely cure is impossible, all surgery and therapy treatments are ineffective. The mortality rate is quite high, the median survival time of GBM is approximately only 1-2 years. Cell migration and invasion is important in GBM tumour progression, as these processes lead the spreading of these star-shaped tumour cells. There are several signalling pathways involved in these processes, in which phosphoinositide 3-kinase (PI3K) signalling pathway is one of these. Previous study has demonstrated the knockdown of p110δ isoform of class IA PI3K reduces the ability of migration and invasion in GBM cell lines. Furthermore, glioma cells may change the extracellular matrix (ECM) environment by secreting ECM molecules, to provide a suitable matrix for cell adhesion and migration. Among numerous ECM proteins and integrins, a study of p110δ knockdown effect on adhesion molecules/ECM proteins in GBM had narrowed them to five outstanding genes - ITGB3, ITGA5, ITGA7, TGFBI and TIMP1. However, that was just a screening study which lacked validation. In this study, we validated the mRNA expression of two ECM proteins TGFBI and TIMP1, that are significantly down-regulated and exhibits a reduction trend that correlates p110δ knockdown in U87 cell. These results implicated that TGFBI and TIMP1 may involve in the migration and invasion of U87 GBM cells. Although there are still many issues need to be addressed, the results of this study can be collaborated together with other investigations on adhesion molecules to understand more about the molecular mechanisms that are influenced by PI3K. The inter-relationship between ECM proteins and integrins present in the GBM tumour microenvironment may provide a new insight for GBM investigation and for the development of potential specific molecular target therapy to fight against GBM.|
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