Data-independent Proteomic Screen Identifies Novel Tamoxifen Agonist that Mediates Drug Resistance

A label-free quantitative variation of the recently developed data-independent shotgun proteomic method Precursor Acquisition Independent From Ion Count (PAcIFIC) was used to identify novel proteins implicated in cancer progression and resistance. Specifically, this screen identified the pro-metastatic protein anterior gradient 2 (AGR2) as significantly up-regulated in tamoxifen treated cells. Highlighting the need for direct proteome profiling methods like PAcIFIC, neither data-dependent gas-phase fractionation nor a transcriptomic screen detected AGR2 protein/ transcript at significantly up-regulated levels. Further cell-based experiments using human cancer cell lines and in vivo xenografts confirmed the PAcIFIC hypothesis that AGR2 is up-regulated in MCF-7 cells post tamoxifen treatment, and that it is implicated in drug resistance mediation.