Negative regulation of N-cadherin-mediated cell-cell adhesion by the estrogen receptor signaling pathway in rat pituitary GH3 cells

Endocrine. 1999 Feb;10(1):67-76. doi: 10.1385/ENDO:10:1:67.


The ability of the estrogen receptor signaling pathway to regulate cell-cell adhesion, and N-cadherin and beta-catenin expression was examined in rat somatolactotropic GH3 cells cultured in serum-free, phenol red-free medium (SFM). Estradiol-17beta (E2) promoted a nonadherent phenotype, whereas the steroidal antiestrogen, ICI 182,780, induced the formation of tightly adherent aggregates of cells. The antiestrogen-induced cell-cell adhesion was associated with the presence of adherens junctions, and was Ca2+-dependent. E2 reduced surface N-cadherin protein to barely detectable levels, whereas ICI 182,780-treated cells displayed abundant punctate immunoreactive N-cadherin. Antiestrogen failed to induce adhesion in the presence of a blocking antibody to N-cadherin. ICI 182,780 increased the protein levels for N-cadherin and the cadherin-binding protein, beta-catenin, by twofold over SFM controls or E2-treated samples. ICI 182,780 also increased the mRNA levels for N-cadherin and beta-catenin by two- to fivefold. In GH3 cells cultured in growth medium, ICI 182,780 increased N-cadherin and beta-catenin levels by twofold over untreated controls, and inhibited cell proliferation by 53%. These results provide the first demonstration of the regulation of N-cadherin-mediated cell-cell adhesion by the estrogen receptor (ER) signaling pathway in pituitary somatolactotrophs through the coordinate regulation of N-cadherin and beta-catenin expression. The inverse relationship between ICI 182,780-induced adhesion and proliferation raises the possibility that these two processes are functionally related.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Cadherins / metabolism
  • Cadherins / pharmacology*
  • Cell Adhesion*
  • Cell Division / drug effects
  • Cytoskeletal Proteins / metabolism
  • Estradiol / analogs & derivatives
  • Estradiol / pharmacology
  • Fluorescent Antibody Technique
  • Fulvestrant
  • Microscopy, Confocal
  • Microscopy, Electron
  • Pituitary Neoplasms / metabolism
  • Pituitary Neoplasms / pathology*
  • Rats
  • Receptors, Estrogen / physiology*
  • Signal Transduction*
  • Trans-Activators*
  • Tumor Cells, Cultured
  • beta Catenin


  • Antineoplastic Agents
  • Cadherins
  • Ctnnb1 protein, rat
  • Cytoskeletal Proteins
  • Receptors, Estrogen
  • Trans-Activators
  • beta Catenin
  • Fulvestrant
  • Estradiol