Selective estrogen receptor modulator regulated proteins in endometrial cancer cells

Mol Cell Endocrinol. 2004 Apr 30;219(1-2):127-39. doi: 10.1016/j.mce.2004.01.003.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Endometrial Neoplasms / metabolism*
  • Estradiol / pharmacology
  • Female
  • HSP90 Heat-Shock Proteins / genetics
  • HSP90 Heat-Shock Proteins / metabolism
  • Heterogeneous-Nuclear Ribonucleoprotein Group F-H / genetics
  • Heterogeneous-Nuclear Ribonucleoprotein Group F-H / metabolism
  • Humans
  • Keratins / genetics
  • Keratins / metabolism
  • Lactoferrin / genetics
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism
  • Piperidines / pharmacology
  • Receptors, Estrogen / physiology
  • Selective Estrogen Receptor Modulators / pharmacology*
  • Tamoxifen / pharmacology*
  • Ubiquitin-Conjugating Enzymes / genetics
  • Ubiquitin-Conjugating Enzymes / metabolism

Substances

  • Biomarkers
  • Carrier Proteins
  • HSP90 Heat-Shock Proteins
  • Heterogeneous-Nuclear Ribonucleoprotein Group F-H
  • Neoplasm Proteins
  • Phosphoproteins
  • Piperidines
  • RNA polymerase II-binding proteins
  • Receptors, Estrogen
  • Selective Estrogen Receptor Modulators
  • Tamoxifen
  • ritetronium
  • Estradiol
  • Keratins
  • Ubiquitin-Conjugating Enzymes
  • Lactoferrin