Influence of retinoic acid on adhesion complexes in human hepatoma cells: a clue to its antiproliferative effects.
Retinoic acid exerts antiproliferative and differentiative effects in normal and transformed in vitro hepatocytes. In order to verify whether these effects are related to a modulation of adhesion molecules, we used Western blot analysis and immunofluorescence microscopy to investigate the E-cadherinl/beta-catenin complex, the main system of adherens junctions, and the occludin/ZO-1 complex present in the tight junctions in HepG2 cells cultured in the presence or absence of retinoic acid. Results showed that retinoic acid treatment increases the amount of beta-catenin bound to E-cadherin by decreasing its tyrosine-phosphorylation level. Similar results were obtained with the tight junction system, in which the amount of occludin/ZO-1 complex is increased by a similar mechanism that reduced the level of ZO-1 phosphorylation on tyrosine. Immunofluorescence images also confirm these results, showing the localization on the cell surface of both adhesion complexes. Their insertion into the plasma membrane could be suggestive of an optimal reassembly and function of adherens and tight junctions in hepatoma cells, indicating that retinoic acid, besides inhibiting cell proliferation, improves cell-cell adhesion, sustaining or inducing the expression of a more differentiated phenotype.
Ara
Carmen
C
Department of Basic and Applied Biology, University of L'Aquila, L'Aquila, Italy.
Devirgiliis
Laura Conti
LC
Massimi
Mara
M
D015820:Cadherins / Q000032:analysis / Q000187:drug effects / Q000235:genetics; D002448:Cell Adhesion / Q000187:drug effects* / Q000502:physiology; D002455:Cell Division / Q000187:drug effects* / Q000502:physiology; D045744:Cell Line, Tumor; D003598:Cytoskeletal Proteins / Q000032:analysis / Q000187:drug effects / Q000235:genetics; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D046911:Macromolecular Substances / Q000378:metabolism; D008565:Membrane Proteins / Q000032:analysis / Q000187:drug effects / Q000235:genetics; D008856:Microscopy, Fluorescence / Q000379:methods; D062793:Occludin; D010750:Phosphoproteins / Q000032:analysis / Q000187:drug effects / Q000235:genetics; D015534:Trans-Activators / Q000032:analysis / Q000187:drug effects / Q000235:genetics; D014212:Tretinoin / Q000494:pharmacology*; D062826:Zonula Occludens-1 Protein; D051176:beta Catenin
C495270:CTNNB1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; D046911:Macromolecular Substances; D008565:Membrane Proteins; C568985:OCLN protein, human; D062793:Occludin; D010750:Phosphoproteins; C569042:TJP1 protein, human; D015534:Trans-Activators; D062826:Zonula Occludens-1 Protein; D051176:beta Catenin; D014212:Tretinoin