title: Identification of novel proteins induced by estradiol, 4-hydroxytamoxifen and acolbifene in T47D breast cancer cells.
abstract: Tamoxifen is currently used as adjuvant therapy for estrogen receptor (ER) positive breast cancer patients and as a chemopreventative agent. Although ER is a predictive marker for tamoxifen response, ER status fails to predict tamoxifen response in a significant number of patients highlighting the need to identify new pathways for tamoxifen sensitivity/resistance. To identify novel proteins induced by tamoxifen in breast cancer cells sensitive to tamoxifen growth inhibition, two-dimensional (2D) gel electrophoresis was used to profile proteins in T47D breast cancer cells. Six proteins were identified that were differentially regulated by 17beta-estradiol, 4-hydroxytamoxifen and the pure antagonist acolbifene (EM-652); calreticulin, synapse associated protein 1 (SYAP1), CD2 antigen binding protein 2 (CD2BP2), nucleosome assembly protein 1 like 1 (NAP1L1), d-3-phosphoglycerate dehydrogenase (3-PHGDH) and pyridoxine 5' phosphate oxidase (PNPO). At the mRNA level, these ligands differentially regulated expression of mRNAs encoding the identified proteins in T47D and MCF7 cells but had no effect on mRNA in ERalpha-negative MDA-MB-231 breast cancer cells. These novel SERM-regulated proteins may participate in new or existing pathways for sensitivity or resistance to SERMs.
authors.affiliation: Department of Biochemistry and Cancer Biology, Medical University of Ohio, Toledo, OH, USA.
authors.forename: Mariam H
authors.initials: MH
authors.lastname: Al-Dhaheri
authors.forename: Yatrik M
authors.initials: YM
authors.lastname: Shah
authors.forename: Venkatesha
authors.initials: V
authors.lastname: Basrur
authors.forename: Steven
authors.initials: S
authors.lastname: Pind
authors.forename: Brian G
authors.initials: BG
authors.lastname: Rowan
mesh_terms: D000595:Amino Acid Sequence; D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D004958:Estradiol / Q000378:metabolism*; D004965:Estrogen Antagonists / Q000378:metabolism*; D047628:Estrogen Receptor alpha / Q000378:metabolism; D005260:Female; D006801:Humans; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D010880:Piperidines / Q000378:metabolism*; D013629:Tamoxifen / Q000031:analogs & derivatives* / Q000378:metabolism
chemical_list: D004965:Estrogen Antagonists; D047628:Estrogen Receptor alpha; D009363:Neoplasm Proteins; D010880:Piperidines; D013629:Tamoxifen; C016601:afimoxifene; C012121:ritetronium; D004958:Estradiol