Regulation of MYC expression and differential JQ1 sensitivity in cancer cells

Trent Fowler, Payel Ghatak, David H. Price, Ronald Conaway, Joan Conaway, Cheng Ming Chiang, James E. Bradner, Ali Shilatifard, Ananda L. Roy

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Article numbere87003
JournalPLoS One
Volume9
Issue number1
DOIs
StatePublished - Jan 23 2014

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lymphoma
Cells
Positive Transcriptional Elongation Factor B
transcription (genetics)
Neoplasms
Chemical compounds
Burkitt Lymphoma
chemical compounds
cells
Transcription
carcinoma
Tumors
Elongation
Animals
Transcription Factors
transcription factors
animal models
Peptide Elongation Factors
therapeutics
neoplasms

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Fowler, T., Ghatak, P., Price, D. H., Conaway, R., Conaway, J., Chiang, C. M., ... Roy, A. L. (2014). Regulation of MYC expression and differential JQ1 sensitivity in cancer cells. PLoS One, 9(1), [e87003]. https://doi.org/10.1371/journal.pone.0087003

Regulation of MYC expression and differential JQ1 sensitivity in cancer cells. / Fowler, Trent; Ghatak, Payel; Price, David H.; Conaway, Ronald; Conaway, Joan; Chiang, Cheng Ming; Bradner, James E.; Shilatifard, Ali; Roy, Ananda L.

In: PLoS One, Vol. 9, No. 1, e87003, 23.01.2014.

Research output: Contribution to journalArticle

Fowler, T, Ghatak, P, Price, DH, Conaway, R, Conaway, J, Chiang, CM, Bradner, JE, Shilatifard, A & Roy, AL 2014, 'Regulation of MYC expression and differential JQ1 sensitivity in cancer cells', PLoS One, vol. 9, no. 1, e87003. https://doi.org/10.1371/journal.pone.0087003
Fowler, Trent ; Ghatak, Payel ; Price, David H. ; Conaway, Ronald ; Conaway, Joan ; Chiang, Cheng Ming ; Bradner, James E. ; Shilatifard, Ali ; Roy, Ananda L. / Regulation of MYC expression and differential JQ1 sensitivity in cancer cells. In: PLoS One. 2014 ; Vol. 9, No. 1.
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