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Open Access Green as soon as Postprint is submitted to ZB.
Identification of Polo-like kinase 1 as a potential therapeutic target in anaplastic thyroid carcinoma.
Cancer Res. 69, 1916-1923 (2009)
Anaplastic thyroid carcinoma (ATC) is one of the most aggressive and chemoresistant cancers. The serine/threonine kinase Polo-like kinase 1 (PLK1), a key regulator of multiple steps during mitotic progression, is highly expressed in ATC. Here, we used the BI 2536 PLK1 inhibitor on ATC and nontransformed thyroid follicular cell tines. Our data show that ATC cells are addicted to high levels of PLK1 activity for proliferation, survival, anchorage-independent growth, and tumorigenicity. On treatment with nanomolar doses of BI 2536, ATC cells progressed normally through S phase but died thereafter, directly from mitotic arrest. Immunofluorescence microscopy, immunoblot, and flow cytometry analysis showed that, on PLK1 blockade, ATC cells arrested in prometaphase with a 4N DNA content. Treated ATC cells accumulated phosphohistone H3 and displayed characteristic mitotic (Polo) spindle aberrations. Nontransformed thyroid cells were 3.2- to 18.4-fold less susceptible to BI 2536-induced cell cycle effects compared with ATC cells. These findings identify PLK1 as a promising target for the molecular therapy of ATC.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
small-molecule inhibitor; cancer-cells; tumor-growth; pik3ca gene; dna-damage; plk1; mutation; polo-like-kinase-1; depletion; cycle
ISSN (print) / ISBN
0008-5472
e-ISSN
1538-7445
Journal
Cancer Research
Quellenangaben
Volume: 69,
Issue: 5,
Pages: 1916-1923
Publisher
American Association for Cancer Research (AACR)
Publishing Place
Philadelphia, Pa.
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Institute of Molecular Radiation Biology (IMS)