Role of the PARP1/HPF1 complex in the conferring of resistance to doxorubicin in triple negative breast cancer (dataset)

Abstract

Multidrug resistance (MDR) is characterized, inter alia, by overexpression of ABC transporters responsible for the removal of drugs outside the cell and their sequestration in intracellular organelles. Considering that ADP-ribosylation of EP300 plays a key role in the complex-dependent regulation of gene transcription, we set out to test whether inhibition of PARP1 protein activity would affect the repression of ABC transporters. Moreover, our next goal was to identify the transcription factor responsible for PARP1-dependent expression of ABC genes that are important for induction of doxorubicin resistance in the MDA-MB-231 cell line. This dataset provides information obtained by qPCR technique indicating that PARP1 protein inhibition with Olaparib and Veliparib, as well as silencing of components of the PARP1/HPF1 complex, leads to repression of all tested ABCC and ABCG2 proteins in the doxorubicin-resistant MDA-MB-231 line. Furthermore, incubation with selected antioxidants to withdraw genotoxic stress leads to inhibition of the repressive effect of Veliparib on the expression of ABC transporters. Using the ChIP-Seq method, we also identified a transcription factor belonging to the SWI/SNF family, SMARCA1, which is responsible for PARP1-dependent expression of ABCC2, ABCC3, ABCC4 and ABCC5 transporters important for doxorubicin resistance (after publication, data will be available in Sequence Read Archive (SRA)). In the accompanying data set, we showed that for ABCC5, SMARCA1 acted as a transcriptional enhancer. We also confirmed the presence of the SMARCA1 factor in PARP1-rich regions for ABC.