FIG 1. H3K14ac enrichment and histone acetyltransferase expression is altered in olaparib-resistant HGSOC cells and a PDX model.

(A) Histone extracts from the indicated olaparib-sensitive and olaparib-resistant HGSOC cell lines were assayed in triplicate by mass spectrometry for histone modifications. Data are shown for each sensitive/resistant pair as the mean ± SD percentage of acetylated H3K14. N = 3; p-value by t-test. (B) Histone extracts from the indicated olaparib sensitive/resistant pairs were assayed by immunoblot for H3K14ac and total H3. The H3K14ac:H3 ratio was determined by band densitometry and normalized to the olaparib-sensitive line of each pair, which are set as 1. (C) mRNA from the indicated olaparib sensitive/resistant pairs was assayed for HAT expression by RT-qPCR. To demonstrate Fold Change, target gene expression was determined relative to GAPDH and then normalized to Control mice. Each bar represents the mean ± SD of three PCR reactions. p-values by t-test. (D) Human HGSOC PDX cells were injected into NSG mice. After seven days, mice received a 21-day treatment course of intraperitoneal vehicle control or 50 mg/kg olaparib. Following treatment, tumor cells were allowed to recur over an additional 21 days. Upon necropsy, ascites cells were collected. mRNA from ascites cells was analyzed by RT-qPCR for the indicated HATs. To demonstrate Fold Change, target gene expression was determined relative to GAPDH control and then normalized to Control mice. Each bar represents the mean ± SD of three PCR reactions. The numbers below bars are mouse ear tag IDs. p-values were determined by t-test comparing each olaparib-treated mouse (gray bars; #827, #877, #878, or #879) to the average of both control mice (white bars; #834 and #846). * p < 0.05, ** p < 0.01, *** p < 0.001; **** p < 0.0001. Sens = olaparib-sensitive, Res = olaparib-resistant.