Halaka Meena, Hired Zuhaila A, Rutledge Grace E, Hedgepath Carly M, Anderson Michael P, St John Haley, Do Jessica M, Majmudar Parth R, Walker Caleb, Alawawdeh Asma, Stephen Hannah M, Reagor Caleb C, Adereti Jeanette, Jamison Kiara, Iglesias Katherine P, Kirmani Khadija Z, Conway Rebecca E
Department of Biology, College of Liberal Arts and Sciences, Lipscomb University, 1 University Park Drive, Nashville, TN 37204, USA.
J Cancer. 2020 Feb 19;11(9):2688-2701. doi: 10.7150/jca.41004. eCollection 2020.
The endothelins and their receptors are best known for their regulation of the vascular system. Their widespread expression in epithelial cells and their overexpression in some tumors has prompted investigation into their ability to regulate cancer progression. In this study, we assessed the mRNA expression of the major endothelin B receptor gene (EDNRB) isoforms and found differences in both mRNA and protein expression in normal breast cells and breast cancer cell lines. Knocking down the EDNRB gene in breast cancer cells altered invasiveness toward endothelin 3 (ET3), and we observed EDNRB isoform-specific regulation of breast cancer cell invasion and cell signaling, as well as isoform- and subtype-specific differences in breast cancer patient survival. The results reported in this study emphasize the importance of the endothelin B receptor in breast cancer. To our knowledge, this study is the first to clarify the differential expression and roles of specific EDNRB isoforms in breast cancer.
内皮素及其受体因其对血管系统的调节作用而最为人所知。它们在上皮细胞中的广泛表达以及在某些肿瘤中的过度表达促使人们研究它们调节癌症进展的能力。在本研究中，我们评估了主要内皮素B受体基因（EDNRB）亚型的mRNA表达，并发现正常乳腺细胞和乳腺癌细胞系在mRNA和蛋白质表达上均存在差异。敲低乳腺癌细胞中的EDNRB基因会改变其对内皮素3（ET3）的侵袭性，并且我们观察到EDNRB亚型对乳腺癌细胞侵袭和细胞信号传导具有特异性调节作用，以及在乳腺癌患者生存方面存在亚型和亚型特异性差异。本研究报告的结果强调了内皮素B受体在乳腺癌中的重要性。据我们所知，本研究是首次阐明特定EDNRB亚型在乳腺癌中的差异表达及其作用。
