Journal article
Regulation of MYC expression and differential JQ1 sensitivity in cancer cells
PloS one, Vol.9(1), pp.e87003-e87003
2014
DOI: 10.1371/journal.pone.0087003
PMCID: PMC3900694
PMID: 24466310
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.
Details
- Title: Subtitle
- Regulation of MYC expression and differential JQ1 sensitivity in cancer cells
- Creators
- Trent Fowler - Department of Developmental, Molecular and Chemical Biology, Tufts University School of Medicine, Boston, Massachusetts, United States of AmericaPayel Ghatak - Department of Developmental, Molecular and Chemical Biology, Tufts University School of Medicine, Boston, Massachusetts, United States of AmericaDavid H Price - Biochemistry Department, University of Iowa, Iowa City, Iowa, United States of AmericaRonald Conaway - Stowers Institute for Medical Research, Kansas City, Missouri, United States of AmericaJoan Conaway - Stowers Institute for Medical Research, Kansas City, Missouri, United States of AmericaCheng-Ming Chiang - Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas, United States of AmericaJames E Bradner - Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, United States of AmericaAli Shilatifard - Stowers Institute for Medical Research, Kansas City, Missouri, United States of AmericaAnanda L Roy - Department of Developmental, Molecular and Chemical Biology, Tufts University School of Medicine, Boston, Massachusetts, United States of America ; Program in Genetics, Sackler School of Biomedical Science, Tufts University School of Medicine, Boston, Massachusetts, United States of America ; Program in Immunology, Sackler School of Biomedical Science, Tufts University School of Medicine, Boston, Massachusetts, United States of America
- Resource Type
- Journal article
- Publication Details
- PloS one, Vol.9(1), pp.e87003-e87003
- DOI
- 10.1371/journal.pone.0087003
- PMID
- 24466310
- PMCID
- PMC3900694
- NLM abbreviation
- PLoS One
- ISSN
- 1932-6203
- eISSN
- 1932-6203
- Publisher
- Public Library of Science; United States
- Grant note
- R01 CA103867 / NCI NIH HHS R01 GM035500 / NIGMS NIH HHS CA103867 / NCI NIH HHS
- Language
- English
- Date published
- 2014
- Academic Unit
- Biochemistry and Molecular Biology
- Record Identifier
- 9984025290902771
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