Regulation of MYC Expression and Differential JQ1 Sensitivity in Cancer Cells
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Fowler, Trent
Ghatak, Payel
Price, David H.
Conaway, Ronald
Conaway, Joan
Chiang, Cheng-Ming
Shilatifard, Ali
Roy, Ananda L.
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https://doi.org/10.1371/journal.pone.0087003Metadata
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Fowler, Trent, Payel Ghatak, David H. Price, Ronald Conaway, Joan Conaway, Cheng-Ming Chiang, James E. Bradner, Ali Shilatifard, and Ananda L. Roy. 2014. “Regulation of MYC Expression and Differential JQ1 Sensitivity in Cancer Cells.” PLoS ONE 9 (1): e87003. doi:10.1371/journal.pone.0087003. http://dx.doi.org/10.1371/journal.pone.0087003.Abstract
High level MYC expression is associated with almost all human cancers. JQ1, a chemical compound that inhibits MYC expression is therapeutically effective in preclinical animal models in midline carcinoma, and Burkitt’s lymphoma (BL). Here we show that JQ1 does not inhibit MYC expression to a similar extent in all tumor cells. The BL cells showed a ∼90% decrease in MYC transcription upon treatment with JQ1, however, no corresponding reduction was seen in several non-BL cells. Molecularly, these differences appear due to requirements of Brd4, the most active version of the Positive Transcription Elongation Factor B (P-TEFb) within the Super Elongation Complex (SEC), and transcription factors such as Gdown1, and MED26 and also other unknown cell specific factors. Our study demonstrates that the regulation of high levels of MYC expression in different cancer cells is driven by unique regulatory mechanisms and that such exclusive regulatory signatures in each cancer cells could be employed for targeted therapeutics.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3900694/pdf/Terms of Use
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