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

Shawna Mae Hengel, Euan Murray, Simon Langdon, Larry Hayward, Jean O'Donoghue, Alexandre Panchaud, Ted Hupp, David R Goodlett

Research output: Contribution to journalArticlepeer-review

Abstract

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.
Original languageEnglish
Pages (from-to)4567-78
Number of pages12
JournalJournal Of Proteome Research
Volume10
Issue number10
DOIs
Publication statusPublished - 2011

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