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.