Please use this identifier to cite or link to this item:
DC FieldValue
dc.titleCharacterization of the novel role of parkin in Gliomagenesis
dc.contributor.authorYEO WEE SING
dc.identifier.citationYEO WEE SING (2011-07-26). Characterization of the novel role of parkin in Gliomagenesis. ScholarBank@NUS Repository.
dc.description.abstractMutations 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.
dc.subjectParkin, Glioma, VEGFR2, Cyclin D1, Akt, miRNA
dc.contributor.supervisorLIM KAH LEONG
dc.contributor.supervisorLIM TIT MENG
dc.description.degreeconferredDOCTOR OF PHILOSOPHY
Appears in Collections:Ph.D Theses (Open)

Show simple item record
Files in This Item:
File Description SizeFormatAccess SettingsVersion 
YeoWS.pdf2.92 MBAdobe PDF



Google ScholarTM


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.