Transcriptional regulation of IRS5/DOK4 expression in non-small-cell lung cancer cells

Gray, Steven G., Al-Sarraf, Nael, Baird, Anne-Marie, Gately, Kathy, McGovern, Eilish, & O'Byrne, Kenneth J. (2008) Transcriptional regulation of IRS5/DOK4 expression in non-small-cell lung cancer cells. Clinical Lung Cancer, 9(6), pp. 367-374.

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The insulin-receptor substrate family plays important roles in cellular growth, signaling, and survival. Two new members of this family have recently been isolated: IRS5/Dok4 and IRS6/Dok5. This study examines the expression of IRS5/DOK4 in a panel of lung cancer cell lines and tumor specimens. The results demonstrate that expression of IRS5/DOK4 is frequently altered with both elevated and decreased expression in non-small-cell lung cancer (NSCLC) tumor specimens. The altered expression of IRS5/DOK4 observed in tumor samples is not due to aberrant methylation. In vitro cell culture studies demonstrate that treatment of NSCLC cell lines with the histone deacetylase inhibitor trichostatin A (TSA) upregulates IRS5/DOK4. This finding indicates that expression is regulated epigenetically at the level of chromatin remodeling. Chromatin immunoprecipitation experiments confirm that the IRS5/DOK4 promoter has enhanced histone hyperacetylation following treatments with TSA. Finally, hypoxia was demonstrated to downregulate IRS5/DOK4 expression. This expression was restored by TSA. The clinical relevance of altered IRS5/DOK4 expression in NSCLC requires fur ther evaluation.

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ID Code: 65122
Item Type: Journal Article
Refereed: Yes
Additional URLs:
Keywords: Acetylation, Chromatin, DNA methylation, Histone, histone deacetylase inhibitor, insulin receptor substrate 1, insulin receptor substrate 5, trichostatin A, unclassified drug, article, cancer cell culture, cell hypoxia, chromatin assembly and disassembly, chromatin immunoprecipitation, epigenetics, human, human cell, in vitro study, lung non small cell cancer, promoter region, protein blood level, protein expression, protein family, protein isolation, protein methylation, receptor down regulation, receptor upregulation, tissue section, transcription regulation, Adenocarcinoma, Base Sequence, Bronchi, Carcinoma, Non-Small-Cell Lung, Carcinoma, Squamous Cell, Cell Line, Tumor, Cell Proliferation, Enzyme Inhibitors, Gene Expression Regulation, Neoplastic, Histone Deacetylases, Histones, Humans, Hydroxamic Acids, Intracellular Signaling Peptides and Proteins, Lung, Lung Neoplasms, Molecular Sequence Data, Promoter Regions, Genetic, Reverse Transcriptase Polymerase Chain Reaction, RNA, Messenger, Transcription, Genetic
DOI: 10.3816/CLC.2008.n.053
ISSN: 1525-7304
Divisions: Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2008 Elsevier Inc.
Deposited On: 05 Dec 2013 00:51
Last Modified: 29 Jul 2014 23:56

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