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| Status |
Public on Mar 15, 2012 |
| Title |
Parkin pathway activation mitigates glioma cell proliferation and predicts patient survival |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Mutations in the parkin gene, which encodes a ubiquitin ligase, are a major genetic cause of parkinsonism. Interestingly, parkin also plays a role in cancer as a putative tumor suppressor, and the gene is frequently targeted by deletion and inactivation in human malignant tumors. Here, we investigated a potential tumor suppressor role for parkin in gliomas. We found that parkin expression was dramatically reduced in glioma cells. Restoration of parkin expression promoted G1 phase cell cycle arrest and mitigated the proliferation rate of glioma cells in vitro and in vivo. Notably, 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 suppressionof these changes following parkin re-introduction. Clinically, analysis of parkin pathway activation was predictive for the survival outcome of glioma patients. 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 brain tumor patients.
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| Overall design |
Total RNA obtained from U-87MG cells stably expressing parkin or vector alone. Replicate arrays were performed for each of the 3 vector and parkin-expressing U-87MG clones.
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| Contributor(s) |
Yeo CW, Ng FS, Chai C, Tan J, Koh GR, Chong Y, Koh LW, Foong C, Sandanaraj E, Holbrook JD, Ang B, Ryosuke T, Tang C, Lim K |
| Citation(s) |
22431710 |
| Submission date |
May 24, 2011 |
| Last update date |
Jul 26, 2018 |
| Contact name |
Felicia Ng |
| Organization name |
Cambridge Institute for Medical Research
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| Street address |
Wellcome Trust/MRC Building, Addenbrooke's Hospital, Hills Road
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| City |
Cambridge |
| ZIP/Postal code |
CB3 9BB |
| Country |
United Kingdom |
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| Platforms (1) |
| GPL6244 |
[HuGene-1_0-st] Affymetrix Human Gene 1.0 ST Array [transcript (gene) version] |
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| Samples (21)
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| Relations |
| BioProject |
PRJNA141657 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE29494_RAW.tar |
88.8 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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