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SORORIN and PLK1 as potential therapeutic targets in malignant pleural mesothelioma.

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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
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.
Type: article
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)

Submitter: 氏家 秀樹

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