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J Proteome Res. 2011 Oct 7;10(10):4567-78. doi: 10.1021/pr2004117. Epub 2011 Sep 21.

Data-independent proteomic screen identifies novel tamoxifen agonist that mediates drug resistance.

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Department of Medicinal Chemistry, University of Washington , Box 357610, Seattle, Washington 98195-7610, United States.


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.

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