title: Data-independent proteomic screen identifies novel tamoxifen agonist that mediates drug resistance.
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.
authors.affiliation: Department of Medicinal Chemistry, University of Washington , Box 357610, Seattle, Washington 98195-7610, United States.
authors.forename: Shawna Mae
authors.initials: SM
authors.lastname: Hengel
authors.forename: Euan
authors.initials: E
authors.lastname: Murray
authors.forename: Simon
authors.initials: S
authors.lastname: Langdon
authors.forename: Larry
authors.initials: L
authors.lastname: Hayward
authors.forename: Jean
authors.initials: J
authors.lastname: O'Donoghue
authors.forename: Alexandre
authors.initials: A
authors.lastname: Panchaud
authors.forename: Ted
authors.initials: T
authors.lastname: Hupp
authors.forename: David R
authors.initials: DR
authors.lastname: Goodlett
mesh_terms: D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D008956:Models, Chemical; D009088:Mucoproteins; D009368:Neoplasm Transplantation; D015513:Oncogene Proteins; D011506:Proteins / Q000378:metabolism; D040901:Proteomics / Q000379:methods*; D013629:Tamoxifen / Q000494:pharmacology*
chemical_list: C502296:AGR2 protein, human; D018931:Antineoplastic Agents, Hormonal; D009088:Mucoproteins; D015513:Oncogene Proteins; D011506:Proteins; D013629:Tamoxifen