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Title: Parkin pathway activation mitigates glioma cell proliferation and predicts patient survival
Authors: Yeo, C.W.S.
Ng, F.S.L.
Chai, C. 
Tan, J.M.M.
Koh, G.R.H.
Chong, Y.
Koh, L.W.H.
Foong, C.S.F.
Sandanaraj, E.
Holbrook, J.D.
Ang, B.-T. 
Takahashi, R.
Tang, C.
Lim, K.-L. 
Issue Date: 15-May-2012
Citation: Yeo, C.W.S., Ng, F.S.L., Chai, C., Tan, J.M.M., Koh, G.R.H., Chong, Y., Koh, L.W.H., Foong, C.S.F., Sandanaraj, E., Holbrook, J.D., Ang, B.-T., Takahashi, R., Tang, C., Lim, K.-L. (2012-05-15). Parkin pathway activation mitigates glioma cell proliferation and predicts patient survival. Cancer Research 72 (10) : 2543-2553. ScholarBank@NUS Repository.
Abstract: 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 G 1 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 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. ©2012 American Association for Cancer Research.
Source Title: Cancer Research
ISSN: 00085472
DOI: 10.1158/0008-5472.CAN-11-3060
Appears in Collections:Staff Publications

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