Therapeutic Mechanism of BET Bromodomain Inhibitor in Breast Cancer
Annual rept. 15 Aug 2013-14 Aug 2014
DANA-FARBER CANCER INST BOSTON MA
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Genomic profiling of the MCF7 breast cancer cell line using BRD4 ChIP-seq and DNase-seq revealed BRD4 ChIP-seq and DNase-seq to be highly similar. We discovered that the BET inhibitor JQ1 tends to be more effective in slowing the growth of basal rather than luminal breast cancer cell lines. The initial gene expression response of a basal breast cancer cell line, SUM159, on treatment with JQ1, is predominated by the down-regulation of gene expression and this down-regulation is highly associated with BRD4 occupied genomic loci. By 24h of JQ1 treatment secondary effects dominate the gene expression pattern and BRD4 binding no longer predicts gene expression changes. Long-term treatment of SUM159 with JQ1 results in this cell line becoming insensitive to JQ1 and adopting a gene expression pattern that is more luminal-like. This long-term change in gene expression is not highly associated with BRD4 binding.
- Genetic Engineering and Molecular Biology
- Medicine and Medical Research