Negative regulation of N-cadherin-mediated cell-cell adhesion by the estrogen receptor signaling pathway in rat pituitary GH3 cells.
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.
Department of Anatomy, University of Connecticut Health Center, Farmington 06030, USA.
C A
CA
Heinrich
M R
MR
Lail-Trecker
J J
JJ
Peluso
B A
BA
White
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D015820:Cadherins / Q000378:metabolism / Q000494:pharmacology*; D002448:Cell Adhesion; D002455:Cell Division / Q000187:drug effects; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D000077267:Fulvestrant; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D010911:Pituitary Neoplasms / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D011960:Receptors, Estrogen / Q000502:physiology*; D015398:Signal Transduction; D015534:Trans-Activators; D014407:Tumor Cells, Cultured; D051176:beta Catenin
D000970:Antineoplastic Agents; D015820:Cadherins; C495268:Ctnnb1 protein, rat; D003598:Cytoskeletal Proteins; D011960:Receptors, Estrogen; D015534:Trans-Activators; D051176:beta Catenin; D000077267:Fulvestrant; D004958:Estradiol