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- W2068202487 abstract "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 further evaluation." @default.
- W2068202487 created "2016-06-24" @default.
- W2068202487 creator A5011765580 @default.
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- W2068202487 date "2008-11-01" @default.
- W2068202487 modified "2023-09-30" @default.
- W2068202487 title "Transcriptional Regulation of IRS5/DOK4 Expression in Non–Small-Cell Lung Cancer Cells" @default.
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- W2068202487 doi "https://doi.org/10.3816/clc.2008.n.053" @default.
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