Abstract
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.
Copyright 2004 Elsevier Ireland Ltd.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Biomarkers
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Carrier Proteins / genetics
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Carrier Proteins / metabolism
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Endometrial Neoplasms / metabolism*
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Estradiol / pharmacology
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Female
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HSP90 Heat-Shock Proteins / genetics
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HSP90 Heat-Shock Proteins / metabolism
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Heterogeneous-Nuclear Ribonucleoprotein Group F-H / genetics
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Heterogeneous-Nuclear Ribonucleoprotein Group F-H / metabolism
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Humans
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Keratins / genetics
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Keratins / metabolism
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Lactoferrin / genetics
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Neoplasm Proteins / genetics
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Neoplasm Proteins / metabolism*
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Phosphoproteins / genetics
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Phosphoproteins / metabolism
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Piperidines / pharmacology
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Receptors, Estrogen / physiology
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Selective Estrogen Receptor Modulators / pharmacology*
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Tamoxifen / pharmacology*
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Ubiquitin-Conjugating Enzymes / genetics
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Ubiquitin-Conjugating Enzymes / metabolism
Substances
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Biomarkers
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Carrier Proteins
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HSP90 Heat-Shock Proteins
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Heterogeneous-Nuclear Ribonucleoprotein Group F-H
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Neoplasm Proteins
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Phosphoproteins
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Piperidines
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RNA polymerase II-binding proteins
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Receptors, Estrogen
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Selective Estrogen Receptor Modulators
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Tamoxifen
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ritetronium
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Estradiol
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Keratins
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Ubiquitin-Conjugating Enzymes
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Lactoferrin