Abstract
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.
Highlights
Breast cancer (BCa) has become one of the most common cancer among women, with nearly 200,000 new cases diagnosed each year [1]
CAPER protein expression was assessed by immunohistochemistry within 192 estrogen receptor (ER)+, 48 human epidermal growth factor receptor 2 (HER2)+ and 116 TN breast cancers compared to 94 normal human breast tissue samples (Figure 1A)
Our results revealed a significant increase of CAPER expression in all major breast cancer subtypes when compared to normal healthy breast specimens (Figure 1B; ER+; 2.5-fold, p < 0.001, n = 192; HER2+; 1.7-fold, p < 0.05, n = 48; triple negative breast cancers (TNBCs); 2-fold, p < 0.001, n = 116)
Summary
Breast cancer (BCa) has become one of the most common cancer among women, with nearly 200,000 new cases diagnosed each year [1]. This diverse disease becomes a major cause of death in women of all ages and ethnicities. Triple negative breast cancer (TNBC) is defined by its lack of ER, PR, and HER2 receptors expression. These TNBCs are poorly differentiated and transition quickly to a more aggressive metastatic course than any other BCa subtypes, leading to worst prognosis and shortest survival rates [2, 3]. Targeted therapy for TNBC patients has become an important research focus and many clinical trials are underway to target DNA repair pathways [7]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
