1. ¹Department of Dental Laboratory Technology, Central Taiwan University of Science and Technology, Taichung, Taiwan
2. ²Feng-Yuan Hospital, Feng-Yuan, Taiwan
3. ³Graduate Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan
4. ⁴Department of Pathology, China Medical University Hospital, Taichung, Taiwan
5. ⁵Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan
6. ⁶Division of Thoracic Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan

Correspondence: Professor K-C Chow, PhD, Graduate Institute of Biomedical Sciences, National Chung Hsing University, 250 Kuo-Kuang Road, Taichung 40227, Taiwan. E-mail: kcchow@dragon.nchu.edu.tw

^*These authors contributed equally to this work.

Received 12 January 2009; Revised 22 April 2009; Accepted 23 April 2009; Published online 12 June 2009.

Abstract

Dynamin-related protein 1 (DRP1), an 80 kDa GTPase, is involved in mitochondrial fission and anticancer drug-mediated cytotoxicity, which implicate an association with disease progression of cancer. In this study we investigated the prognostic value of DRP1 in lung adenocarcinomas. Using immunohistochemistry, we measured the expression of DRP1 in 227 patients with lung adenocarcinomas. Expression of DRP1 was confirmed by immunoblotting. The correlation between DRP1 expression and clinicopathological parameters was analyzed by statistical analysis. Difference of survivals between different groups was compared by a log-rank test. The results showed that DRP1 expression was detected in 202 patients with lung adenocarcinomas. Among these, nuclear DRP1 (DRP1^nuc) was detected in 184 patients. A significant difference was found in cumulative survival between patients with high DRP1^nuc levels and those with DRP1^cyt levels (P<0.001). In vitro, hypoxia increased DRP1^nuc levels and cisplatin resistance. Antibodies specific to DRP1 co-precipitated a human homologue of yeast Rad23 protein A (hHR23A) and silencing of hHR23A decreased the nuclear DRP1 level and cisplatin resistance. In conclusion, DRP1^nuc is highly expressed in lung adenocarcinomas, and correlates with poor prognosis. Nuclear DRP1 may increase drug resistance during hypoxia, and hHR23A is essential for nuclear transportation of DRP1. Our results suggest that other than the protein level alone, intracellular distribution of the protein is critical for determining the protein function in cells.