Selective estrogen receptor modulator regulated proteins in endometrial cancer cells.
Tamoxifen is the primary hormonal therapy for breast cancer and is also used as a breast cancer chemopreventative agent. A major problem with tamoxifen therapy is undesirable endometrial proliferation. To identify proteins associated with the growth stimulatory effects of tamoxifen in an ER-positive model, the present study profiled total cellular and secreted proteins regulated by estradiol and selective estrogen receptor modifiers (SERMs) in the Ishikawa endometrial adenocarcinoma cell line using two-dimensional gel electrophoresis. Following 24 h incubation with 10(-8) M estradiol, 10(-7) M 4-hydroxytamoxifen, or 10(-7) M EM-652 (Acolbifene), nine proteins exhibited significant increase in expression. The proteins identified were heat shock protein 90-alpha, and -beta, heterogeneous nuclear ribonucleoprotein F, RNA polymerase II-mediating protein, cytoskeletal keratin 8, cytoskeletal keratin 18, ubiquitin-conjugating enzyme E2-18 kDa and nucleoside diphosphate kinase B. These protein profiles may serve as novel indices of SERM response and may also provide insight into novel mechanisms of SERM-mediated growth.
Shah
Yatrik M
YM
Department of Biochemistry & Molecular Biology, Medical College of Ohio, 3035 Arlington Avenue, Toledo, OH 43614-5804, USA.
Basrur
Venkatesha
V
Rowan
Brian G
BG
D015415:Biomarkers; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D016889:Endometrial Neoplasms / Q000378:metabolism*; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D018841:HSP90 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D034541:Heterogeneous-Nuclear Ribonucleoprotein Group F-H / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007633:Keratins / Q000235:genetics / Q000378:metabolism; D007781:Lactoferrin / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology; D011960:Receptors, Estrogen / Q000502:physiology; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology*; D013629:Tamoxifen / Q000494:pharmacology*; D044763:Ubiquitin-Conjugating Enzymes / Q000235:genetics / Q000378:metabolism
D015415:Biomarkers; D002352:Carrier Proteins; D018841:HSP90 Heat-Shock Proteins; D034541:Heterogeneous-Nuclear Ribonucleoprotein Group F-H; D009363:Neoplasm Proteins; D010750:Phosphoproteins; D010880:Piperidines; C046282:RNA polymerase II-binding proteins; D011960:Receptors, Estrogen; D020845:Selective Estrogen Receptor Modulators; D013629:Tamoxifen; C012121:ritetronium; D004958:Estradiol; D007633:Keratins; D044763:Ubiquitin-Conjugating Enzymes; D007781:Lactoferrin