CAPER as a therapeutic target for triple negative breast cancer
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Mallory C. Campbell1, Laura Pontiggia2, Ashley Y. Russell1, Roland Schwarting3, Jeanette Camacho3, Jean-Francois Jasmin1 and Isabelle Mercier1,4
1Department of Pharmaceutical Sciences, Philadelphia College of Pharmacy, University of the Sciences, Philadelphia, PA 19104, USA
2Department of Mathematics, Physics and Statistics, Misher College of Arts and Sciences, University of the Sciences, Philadelphia, PA 19104, USA
3Department of Pathology, Cooper University Hospital, Camden, NJ 08103, USA
4Program in Personalized Medicine and Targeted Therapeutics, University of the Sciences, Philadelphia, PA 19104, USA
Isabelle Mercier, email: firstname.lastname@example.org
Keywords: breast cancer; oncology targets; triple negative breast cancer; DNA repair
Received: April 28, 2018 Accepted: June 13, 2018 Published: July 13, 2018
Breast cancers (BCas) that lack expression of the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) are referred to as triple negative breast cancers (TNBCs) and have the poorest clinical outcome. Once these aggressive tumors progress to distant organs, the median survival decreases to 12 months. With endocrine therapies being ineffective in this BCa subtype, highly toxic chemo- and radiation therapies are the only options. A better understanding of the functional role(s) of molecular targets contributing to TNBC progression could help in the design and development of new treatments that are more targeted with less toxicity. CAPER (Co-activator of AP-1 and ER) is a nuclear transcriptional co-activator that was recently involved in ER-positive BCa progression, however its role in hormone-independent cancers remains unknown. Our current report demonstrates that CAPER expression is upregulated in human TNBC specimens compared to normal breast tissue and that its selective downregulation through a lentiviral-mediated shRNA knockdown approach resulted in decreased cell numbers in MDA-MB-231 and BT549 TNBC cell lines without affecting the growth of non-tumorigenic cell line MCF-10A. Concordant with these observations, CAPER knockdown was also associated with a decrease in DNA repair proteins leading to a marked increase in apoptosis, through caspase-3/7 activation without any changes in cell cycle. Collectively, we propose CAPER as an important signaling molecule in the development of TNBC linked to DNA repair mechanisms, which could lead to new therapeutic modalities for the treatment of this aggressive cancer.
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