title: 17Beta-estradiol induces down-regulation of Cap43/NDRG1/Drg-1, a putative differentiation-related and metastasis suppressor gene, in human breast cancer cells.
abstract: OBJECTIVE
  Cap43 is known as a nickel- and calcium-inducible gene. In the present study, we examined whether 17beta-estradiol (E2) could affect the expression of Cap43 in breast cancer.
  
  
  METHODS
  Real-time PCR, immunoblotting, and immunocytochemistry were used to examine the expression of Cap43 and estrogen receptor-alpha (ER-alpha) in breast cancer cell lines. MDA-MB-231 and SK-BR-3 cell lines were transfected with ER-alpha cDNA to establish cells overexpressing ER-alpha. Immunohistochemistry was used to evaluate the expression of the Cap43 protein in breast cancer patients (n = 96), and the relationship between Cap43 expression and clinicopathologic findings was examined.
  
  
  RESULTS
  Of the eight cell lines, four expressed higher levels of Cap43 with very low levels of ER-alpha, whereas the other four expressed lower levels of Cap43 with high ER-alpha levels. Treatment with E2 decreased the expression of Cap43 dose-dependently in ER-alpha-positive cell lines but not in ER-alpha-negative lines. Administration of antiestrogens, tamoxifen and ICI 182780, abrogated the E2-induced down-regulation of Cap43. Overexpression of ER-alpha in both ER-alpha-negative cell lines, SK-BR-3 and MDA-MB-231, resulted in down-regulation of Cap43. Immunostaining studies showed a significant correlation between Cap43 expression and the histologic grade of tumors (P = 0.0387). Furthermore, Cap43 expression was inversely correlated with the expression of ER-alpha (P = 0.0374).
  
  
  CONCLUSIONS
  E2-induced down-regulation of Cap43 seems to be mediated through ER-alpha-dependent pathways in breast cancer cells both in culture and in patients. Cap43 has potential as a molecular marker to determine the therapeutic efficacy of antiestrogenic anticancer agents in breast cancer.
authors.affiliation: Center for Innovative Cancer Therapy of the 21st Century Center of Excellence Program for Medical Science and Departments of Surgery and Pathology, Kurume University, Kurume, Fukuoka, Japan.
authors.forename: Abbas
authors.initials: A
authors.lastname: Fotovati
authors.forename: Teruhiko
authors.initials: T
authors.lastname: Fujii
authors.forename: Miki
authors.initials: M
authors.lastname: Yamaguchi
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Kage
authors.forename: Kazuo
authors.initials: K
authors.lastname: Shirouzu
authors.forename: Shinji
authors.initials: S
authors.lastname: Oie
authors.forename: Yuji
authors.initials: Y
authors.lastname: Basaki
authors.forename: Mayumi
authors.initials: M
authors.lastname: Ono
authors.forename: Hideaki
authors.initials: H
authors.lastname: Yamana
authors.forename: Michihiko
authors.initials: M
authors.lastname: Kuwano
mesh_terms: D018797:Cell Cycle Proteins; D049109:Cell Proliferation; D015536:Down-Regulation; D004958:Estradiol / Q000502:physiology*; D004965:Estrogen Antagonists / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000032:analysis; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology; D016133:Polymerase Chain Reaction; D011506:Proteins / Q000032:analysis* / Q000187:drug effects; D013629:Tamoxifen / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D000099259:N-myc Downstream-Regulated Gene 1 Protein
chemical_list: D018797:Cell Cycle Proteins; D004958:Estradiol; D004965:Estrogen Antagonists; D047628:Estrogen Receptor alpha; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; D013629:Tamoxifen; D000099259:N-myc Downstream-Regulated Gene 1 Protein