J Cancer 2020; 11(9):2688-2701. doi:10.7150/jca.41004 This issue

Research Paper

Differences in Endothelin B Receptor Isoforms Expression and Function in Breast Cancer Cells

Meena Halaka, Zuhaila A. Hired, Grace E. Rutledge, Carly M. Hedgepath, Michael P. Anderson, Haley St. John, Jessica M. Do, Parth R. Majmudar, Caleb Walker, Asma Alawawdeh, Hannah M. Stephen, Caleb C. Reagor, Jeanette Adereti*, Kiara Jamison*, Katherine P. Iglesias*, Khadija Z. Kirmani*, Rebecca E. Conway

Department of Biology, College of Liberal Arts and Sciences, Lipscomb University, 1 University Park Drive, Nashville, TN 37204, USA
*These authors contributed equally to the work.

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Citation:
Halaka M, Hired ZA, Rutledge GE, Hedgepath CM, Anderson MP, St. John H, Do JM, Majmudar PR, Walker C, Alawawdeh A, Stephen HM, Reagor CC, Adereti J, Jamison K, Iglesias KP, Kirmani KZ, Conway RE. Differences in Endothelin B Receptor Isoforms Expression and Function in Breast Cancer Cells. J Cancer 2020; 11(9):2688-2701. doi:10.7150/jca.41004. Available from https://www.jcancer.org/v11p2688.htm

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Abstract

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.