Abstract 1427: Investigating role of RECQ1 in response to gemcitabine treatment in triple negative breast cancer

Abstract The response of cancer cells to therapeutic drugs aimed at causing DNA damage is dependent on proteins that play roles in DNA repair. Single nucleotide polymorphism in RECQ1 (also known as RECQL or RECQL1), a DNA helicase involved in DNA damage and replication stress response, is reported to influence patient’s response to gemcitabine in pancreatic cancer leading to poor survival. Gemcitabine is also used as a chemotherapeutic against triple negative breast cancer; however resistance to gemcitabine is reported. The mechanism by which gemcitabine chemoresistance is obtained is poorly understood. Given the importance of RECQ1 in replication fork restart and it being categorized as a breast cancer susceptibility gene, we wish to investigate the role of RECQ1 in modulating cellular response to gemcitabine in triple negative breast cancer cells. To study RECQ1 functions, we developed isogenic pairs of RECQ1-proficient and RECQ1-deficient cells by CRISPR-Cas9-mediated targeted inactivation of RECQ1 in breast cancer cell lines as in vitro model system. RECQ1-knockout MDA-MB-231 cells displayed reduced cell growth and proliferation, and increased DNA damage as compared to the MDA-MB-231 cells expressing wild type RECQ1. As compared to RECQ1-proficient MDA-MB-231 cells, RECQ1-deficient cells were more sensitive to gemcitabine treatment, incurred significantly greater load of double strand breaks upon gemcitabine treatment, and displayed aberrant cell cycle progression following recovery from gemcitabine treatment. Our ongoing experiments are investigating the detailed mechanism of RECQ1’s role in response to gemcitabine and its implications in therapeutic response. Funding: This work was funded by the NIGMS/NIH grant SC1GM093999 to Sudha Sharma. We also acknowledge support from the NIMHD/NIH award number G12MD007597 and NIA/NIH award number 1R25 AG047843-02. We thank Drs. Ritu Chaudhary, Xiaoling Li and Ashish Lal (NCI) for their help and support. Citation Format: Swetha Parvathaneni, Xing Lu, Sudha Sharma. Investigating role of RECQ1 in response to gemcitabine treatment in triple negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1427. doi:10.1158/1538-7445.AM2017-1427