A tale of two antibodies. Trace amine-associated receptor 1 in breast cancer.

Trace amine-associated receptor 1 (TAAR1) is a G protein-coupled receptor only found in vertebrate species. In 2017, it was reported that TAAR1 protein levels in breast cancer samples exhibited a positive correlation with survival, but also were positively correlated with Her2 over-expression. This was surprising as a role for TAAR1 had not previously been suspected either in breast tissue or in cancer. This seminar will outline our attempts to independently validate this previous work. In short, we were unable to replicate the previous findings of a correlation between TAAR1 and Her2 over-expression at either the mRNA or protein levels. This lack of replication has been shown to be due to a lack of selective binding by the commercial anti-TAAR1 antibody used in the initial study, and as such serves as a warning against assuming commercially available antibodies have been appropriately validated. Using a thoroughly-validated antibody we have now confirmed that TAAR1 protein levels are highly variable between commonly used breast cancer cell lines of different molecular phenotypes. Furthermore, we confirm that TAAR1 predominantly resides intracellularly, but that the precise sub-cellular distribution is also variable across cell lines. We show for the first time that in some cell lines TAAR1 is primarily localized to the nucleus. Studies are underway to better understand the roles that TAAR1 activation might play in breast cancer cells.