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Abstract

GTPase hGBP-1 involvement in glioblastoma malignancy

Glioblastoma Multiforme is a stage IV brain cancer arising from astrocytes. EGF receptors (EGFRs) are amplified or constitutively active in 40-50% of glioblastomas. Matrix Metalloproteinase-1, a secreted collagenase involved in tumor invasion, is induced by EGFR in glioblastomas. This induction requires the EGFR-mediated induction of the GTPase, hGBP-1, which increases glioblastoma invasiveness. hGBP-1 is over-expressed in temozolomide (TMZ) resistant U251 glioblastoma cells. To investigate a potential role for hGBP-1 in TMZ-resistance, the level of hGBP-1 was artificially raised in TMZ-sensitive U251 cells and their sensitivity to TMZ was evaluated by colony forming assays. However, there was no difference in survival for the hGBP-1 over-expressing cells compared to the sensitive U251 cells, suggesting hGBP-1 is not sufficient to promote TMZ resistance.  TMZ can also promote autophagy and hGBP-1 can be associated with vesicular structures containing intracellular pathogens. To determine whether hGBP-1 associates with autophagic vesicles, SNB75 glioblastoma cells were transfected with the pEGFP-LC3 plasmid which expresses GFP fused to LC3, a marker for autophagosomes. After 48 hours of serum deprivation, indirect immunofluorescence was used to localize the hGBP-1. Confocal microscopy revealed the co-localization of hGBP-1 and LC3, indicating that hGBP-1 can be involved in autophagy in glioblastomas.

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