2012年5月15日
Parkin pathway activation mitigates glioma cell proliferation and predicts patient survival.
Cancer research
- 巻
- 72
- 号
- 10
- 開始ページ
- 2543
- 終了ページ
- 53
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1158/0008-5472.CAN-11-3060
- 出版者・発行元
- AMER ASSOC CANCER RESEARCH
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.
- リンク情報
- ID情報
-
- DOI : 10.1158/0008-5472.CAN-11-3060
- ISSN : 0008-5472
- eISSN : 1538-7445
- PubMed ID : 22431710
- Web of Science ID : WOS:000307346800010