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Title: Characterization of the novel role of parkin in Gliomagenesis
Keywords: Parkin, Glioma, VEGFR2, Cyclin D1, Akt, miRNA
Issue Date: 26-Jul-2011
Citation: YEO WEE SING (2011-07-26). Characterization of the novel role of parkin in Gliomagenesis. ScholarBank@NUS Repository.
Abstract: Mutations in the parkin gene, which encodes a ubiquitin ligase, has been implicated as one of causative factor for genetic parkinsonism. Interestingly, parkin role has also been implicated in cancer as a putative tumor suppressor with the gene been frequently targeted by deletion and inactivation in several human malignant tumors. Here, we demonstrated a potential tumor suppressor role for parkin in gliomas. We found that parkin expression was dramatically reduced in glioma cells and that the restoration of parkin expression promoted G1 phase cell-cycle arrest and mitigated the proliferation rate of glioma cells in vitro and in vivo. Furthermore, parkin-expressing glioma cells showed a reduction in levels of cyclin D1, but not cyclin E, and a selective downregulation of Akt serine-473 phosphorylation and VEGF receptor levels. In accordance, cells derived from a parkin-null mouse model exhibited increased levels of cyclin D1, VEGF receptor, and Akt phosphorylation, and divided significantly faster when compared with wild-type cells, with suppression of these changes following parkin reintroduction. Clinically, analysis of parkin pathway activation was predictive for the survival outcome of patients with glioma. Taken together, our study provides mechanistic insight into the tumor suppressor function of parkin in brain tumors and suggests that measurement of parkin pathway activation may be used clinically as a prognostic tool in patients with brain tumor.
Appears in Collections:Ph.D Theses (Open)

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