Dicoumarol down-regulates human PTTG1/Securin mRNA expression through inhibition of Hsp90
9 páginas, 5 figuras. Supplementary material for this article is available at Molecular Cancer Therapeutics Online (http://mct.aacrjournals.org/).
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| Format: | artículo biblioteca |
| Language: | English |
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American Association for Cancer Research
2008-03
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| Subjects: | Coumarins, Chaperone, Apoptosis, Gene regulation, Neoplasm proteins, Dicumarol, Anticoagulants, Pituitary tumor-transforming proteins, |
| Online Access: | http://hdl.handle.net/10261/41557 http://dx.doi.org/10.13039/501100011011 |
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dig-irnas-es-10261-415572020-05-25T07:17:27Z Dicoumarol down-regulates human PTTG1/Securin mRNA expression through inhibition of Hsp90 Hernández, Agustín López-Lluch, Guillermo Bernal, Juan Antonio Navas, Plácido Pintor-Toro, José Antonio Ministerio de Educación (España) Junta de Andalucía Coumarins Chaperone Apoptosis Gene regulation Neoplasm proteins Dicumarol Anticoagulants Pituitary tumor-transforming proteins 9 páginas, 5 figuras. Supplementary material for this article is available at Molecular Cancer Therapeutics Online (http://mct.aacrjournals.org/). Securin, the natural inhibitor of sister chromatid untimely separation, is a protooncogene overexpressed in tumors. Its protein levels correlate with malignancy and metastatic proneness. Dicoumarol, a long-established oral anticoagulant, is a new Hsp90 inhibitor that represses PTTG1/Securin gene expression and provokes apoptosis through a complex trait involving both intrinsic and extrinsic pathways. Dicoumarol activity as an Hsp90 inhibitor is confirmed by smaller levels of Hsp90 clients in treated cells and inhibition of in vivo heat shock luciferase activity recovery assays. Likewise, established Hsp90 inhibitors (17-allylamino-geldanamycin and novobiocin) repress PTTG1/Securin gene expression. Also, overexpression of human Hsp90 in yeast makes them hypersensitive to dicoumarol. Both apoptosis and PTTG1/Securin gene repression exerted by dicoumarol in cancer cells are independent of three of the most important signaling pathways affected by Hsp90 inhibition: nuclear factor-kappaB, p53, or Akt/protein kinase B signaling pathways. However, effects on PTTG1/Securin could be partially ascribed to inhibition of the Ras/Raf/extracellular signal-regulated kinase pathway. Overall, we show that expression of PTTG1/Securin gene is Hsp90 dependent and that dicoumarol is a bona fide Hsp90 inhibitor. These findings are important to understand the mode of action of Hsp90 inhibitors, mechanisms of action of dicoumarol, and Securin overexpression in tumors. Spanish Ministry of Education grants SAF02-0264-C03-02 and SAF2005-07713-C03-02; Andalusian Regional Government Grant-in-Aid for Incorporation of Researchers (A. Hernández). Peer reviewed 2011-10-21T10:37:04Z 2011-10-21T10:37:04Z 2008-03 artículo http://purl.org/coar/resource_type/c_6501 Molecular Cancer Therapeutics 7(3): 474-482 (2008) 1535-7163 PMID: 18347135 http://hdl.handle.net/10261/41557 10.1158/1535-7163.MCT-07-0457 1538-8514 http://dx.doi.org/10.13039/501100011011 en http://dx.doi.org/10.1158/1535-7163.MCT-07-0457 none American Association for Cancer Research |
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| topic |
Coumarins Chaperone Apoptosis Gene regulation Neoplasm proteins Dicumarol Anticoagulants Pituitary tumor-transforming proteins Coumarins Chaperone Apoptosis Gene regulation Neoplasm proteins Dicumarol Anticoagulants Pituitary tumor-transforming proteins |
| spellingShingle |
Coumarins Chaperone Apoptosis Gene regulation Neoplasm proteins Dicumarol Anticoagulants Pituitary tumor-transforming proteins Coumarins Chaperone Apoptosis Gene regulation Neoplasm proteins Dicumarol Anticoagulants Pituitary tumor-transforming proteins Hernández, Agustín López-Lluch, Guillermo Bernal, Juan Antonio Navas, Plácido Pintor-Toro, José Antonio Dicoumarol down-regulates human PTTG1/Securin mRNA expression through inhibition of Hsp90 |
| description |
9 páginas, 5 figuras. Supplementary material for this article is available at Molecular Cancer Therapeutics Online (http://mct.aacrjournals.org/). |
| author2 |
Ministerio de Educación (España) |
| author_facet |
Ministerio de Educación (España) Hernández, Agustín López-Lluch, Guillermo Bernal, Juan Antonio Navas, Plácido Pintor-Toro, José Antonio |
| format |
artículo |
| topic_facet |
Coumarins Chaperone Apoptosis Gene regulation Neoplasm proteins Dicumarol Anticoagulants Pituitary tumor-transforming proteins |
| author |
Hernández, Agustín López-Lluch, Guillermo Bernal, Juan Antonio Navas, Plácido Pintor-Toro, José Antonio |
| author_sort |
Hernández, Agustín |
| title |
Dicoumarol down-regulates human PTTG1/Securin mRNA expression through inhibition of Hsp90 |
| title_short |
Dicoumarol down-regulates human PTTG1/Securin mRNA expression through inhibition of Hsp90 |
| title_full |
Dicoumarol down-regulates human PTTG1/Securin mRNA expression through inhibition of Hsp90 |
| title_fullStr |
Dicoumarol down-regulates human PTTG1/Securin mRNA expression through inhibition of Hsp90 |
| title_full_unstemmed |
Dicoumarol down-regulates human PTTG1/Securin mRNA expression through inhibition of Hsp90 |
| title_sort |
dicoumarol down-regulates human pttg1/securin mrna expression through inhibition of hsp90 |
| publisher |
American Association for Cancer Research |
| publishDate |
2008-03 |
| url |
http://hdl.handle.net/10261/41557 http://dx.doi.org/10.13039/501100011011 |
| work_keys_str_mv |
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| _version_ |
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