| Title: | SORORIN and PLK1 as potential therapeutic targets in malignant pleural mesothelioma. |
| Authors: | Kato, Tatsuya Browse this author |
| Lee, Daiyoon Browse this author |
| Wu, Licun Browse this author |
| Patel, Priya Browse this author |
| Young, Ahn Jin Browse this author |
| Wada, Hironobu Browse this author →KAKEN DB |
| Hu, Hsin-Pei Browse this author |
| Ujiie, Hideki Browse this author |
| Kaji, Mitsuhito Browse this author →KAKEN DB |
| Kano, Satoshi Browse this author →KAKEN DB |
| Matsuge, Shinichi Browse this author |
| Domen, Hiromitsu Browse this author |
| Kanno, Hiromi Browse this author |
| Hatanaka, Yutaka Browse this author →KAKEN DB |
| Hatanaka, Kanako C Browse this author |
| Kaga, Kichizo Browse this author →KAKEN DB |
| Matsui, Yoshiro Browse this author →KAKEN DB |
| Matsuno, Yoshihiro Browse this author →KAKEN DB |
| De Perrot, Marc Browse this author |
| Yasufuku, Kazuhiro Browse this author →KAKEN DB |
| Keywords: | SORORIN |
| cell division cycle associated 5 (CDCA5) |
| polo like kinase 1 |
| therapeutic target genes |
| immunohistochemistry |
| malignant pleural mesothelioma |
| Issue Date: | Dec-2016 |
| Journal Title: | International journal of oncology |
| Volume: | 49 |
| Issue: | 6 |
| Start Page: | 2411 |
| End Page: | 2420 |
| Publisher DOI: | 10.3892/ijo.2016.3765 |
| PMID: | 27840913 |
| Abstract: | Malignant pleural mesothelioma (MPM) is an aggressive type of cancer of the thoracic cavity commonly associated with asbestos exposure and a high mortality rate. There is a need for new molecular targets for the development of more effective therapies for MPM. Using quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) and an RNA interference-based screening, we examined the SORORIN gene as potential therapeutic targets for MPM in addition to the PLK1 gene, which is known for kinase of SORORIN. Following in vitro investigation of the effects of target silencing on MPM cells, cell cycle analyses were performed. SORORIN expression was analyzed immunohistochemically using a total of 53 MPM samples on tissue microarray. SORORIN was found to be overexpressed in the majority of clinical MPM samples and human MPM cell lines as determined by qRT-PCR. Gene suppression of each SORORIN and PLK1 led to growth inhibition in MPM cell lines. Knockdown of SORORIN showed an increased number of G2M-phase population and a larger nuclear size, suggesting mitotic arrest. High expression of SORORIN (SORORIN-H) was found in 50.9% of all the MPM cases, and there is a tendency towards poorer prognosis for the SORORIN-H group but the difference is not significant. Suppression of SORORIN with PLK1 inhibitor BI 6727 showed a combinational growth suppressive effect on MPM cell growth. Given high-dose PLK1 inhibitor induced drug-related adverse effects in several clinical trials, our results suggest inhibition SORORIN-PLK1 axis may hold promise for the treatment of MPMs. |
| Rights: | https://creativecommons.org/licenses/by-nc-nd/4.0/ |
| Type: | article |
| URI: | http://hdl.handle.net/2115/76523 |
| Appears in Collections: | 北海道大学病院 (Hokkaido University Hospital) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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