Abstract
We investigated the utility of integrin-linked kinase (ILK) as a target for therapeutic intervention in multiple myeloma (MM). ILK (over-)expression was assessed in primary samples and MM cell lines, and the molecular and physiological consequences of siRNA-mediated ILK ablation were compared to treatment with the small molecule inhibitor QLT0267. Whereas ILK expression was ubiquitous, overexpression was only rarely observed in patient biopsies. ILK knockdown had no effect on the viability or survival pathway activity pattern of MM cells. Conversely, QLT0267 induced cell death in MM cell lines and most primary tumor samples via the intrinsic apoptotic pathway. Although this effect was largely tumor cell-specific it is unlikely to have been mediated via ILK. We conclude that ILK does not play a prominent role in the promotion or sustenance of established MM.
Copyright © 2012 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Azo Compounds / pharmacology
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Cell Death / drug effects
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Cell Death / genetics
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Cell Proliferation / drug effects
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Cell Survival / genetics
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Cells, Cultured
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Dose-Response Relationship, Drug
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Drug Evaluation, Preclinical
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Gene Expression Regulation, Enzymologic / drug effects
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Gene Expression Regulation, Enzymologic / physiology
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Gene Expression Regulation, Neoplastic / drug effects
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Gene Expression Regulation, Neoplastic / physiology
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Gene Knockdown Techniques
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Humans
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Multiple Myeloma / genetics
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Multiple Myeloma / pathology*
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Protein Kinase Inhibitors / pharmacology
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Protein Serine-Threonine Kinases / antagonists & inhibitors
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Protein Serine-Threonine Kinases / genetics
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Protein Serine-Threonine Kinases / physiology*
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Pyrazoles / pharmacology
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RNA, Small Interfering / pharmacology
Substances
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Azo Compounds
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Protein Kinase Inhibitors
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Pyrazoles
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QLT 0267
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RNA, Small Interfering
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integrin-linked kinase
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Protein Serine-Threonine Kinases