Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/16280
Title: Glial cell line-drived neurotrophic factor (GDNF) family of ligands is a mitogenic agent in human glioblastoma and confers chemoresistance in a ligand-specific fashion
Authors: NG WAI HOE
Keywords: GDNF, growth factor, glioma, astrocytoma, brain tumor, chemotherapy
Issue Date: 28-Sep-2007
Source: NG WAI HOE (2007-09-28). Glial cell line-drived neurotrophic factor (GDNF) family of ligands is a mitogenic agent in human glioblastoma and confers chemoresistance in a ligand-specific fashion. ScholarBank@NUS Repository.
Abstract: Malignant gliomas have a universally poor prognosis.Glial Cell-Line Derived Neurotrophic Factor (GDNF) is a neurotrophic factor known to promote neuronal survival of dopaminergic neurons in the embryonic midbrain as well as contribute to carcinogenesis in many cancers. Its ubiquitous presence in central nervous system suggests a role in the mitogenesis of high-grade astrocytoma.GDNF is overexpressed in glioblastoma cell lines and human gliomas. GFRN11b is the predominant spliced isoform in human gliomas and RET9 is the predominant co-receptor. Significantly there is differential overexpression of the GFRN11b spliced isoform compared to the GFRN11a spliced variant.Pre-treatment of glioblastoma cell line with GDNF but not neurturin (NRTN) promoted mitogenic behaviour and conferred chemoresistance to 1,3-Bis(2-chloroethyl)-1-nitrosourea (BCNU). Signaling mapping of BCNU and GDNF suggest that the ability of GDNF to promote Akt activity and inhibit JNK activity may contribute to the increased cellular survival to BCNU chemotherapy. GDNF may therefore be an important mitogenic agent in malignant gliomas.
URI: http://scholarbank.nus.edu.sg/handle/10635/16280
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