This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gniadecki, R. Articles by Hansen, M. Search for Related Content PubMed PubMed Citation Articles by Gniadecki, R. Articles by Hansen, M.

1,25-Dihydroxyvitamin D₃ Stimulates the Assembly of Adherens Junctions in Keratinocytes: Involvement of Protein Kinase C

Department of Dermatological Research, Leo Pharmaceutical Products (R.G.), Ballerup; the Department of Dermatology, University of Copenhagen, Bispebjerg Hospital (R.G.), Copenhagen; and the Microbiology Section, Department of Ecology and Molecular Biology, The Royal Veterinary and Agricultural University (M.H.), Frederiksberg, Denmark; and the Electron Microscopy Laboratory, Polish Academy of Sciences (B.G.), Warsaw, Poland

Address all correspondence and requests for reprints to: Robert Gniadecki, M.D., Ph.D., Department of Dermatology D92, University of Copenhagen, Bispebjerg Hospital, Bispebjerg Bakke 23, 2400 Copenhagen NV, Denmark.

Signaling via intercellular junctions plays an important role in the regulation of growth and differentiation of epithelial cells. Loss of cell-cell contacts has been implicated in carcinogenesis, tumor progression, and metastasis. Here, we investigated whether 1,25-dihydroxyvitamin D₃ [1,25-(OH)₂D₃] was able to stimulate the assembly of adherens junctions and/or desmosomes in cultured human keratinocytes. After 4-day incubation, 1,25-(OH)₂D₃ caused assembly of adherens junctions, but not desmosomes. The adherens junctions were identified upon known ultrastructural criteria and evidence of the translocation of specific junctional proteins (E-cadherin, P-cadherin, -catenin, and vinculin) to the cell-cell borders. The presence of -catenin and vinculin at cell-cell borders indicated that the adherens junctions were functional. This was further supported by showing that anti E-cadherin antibody inhibited the 1,25-(OH)₂D₃-induced keratinocyte stratification. A relation between protein kinase C and adherens junction regulation was noticed. 1,25-(OH)₂D₃-dependent formation of junctions was blocked by the inhibitors of protein kinase C, bisindolylmaleimide and 1-(5-isoquinolinylsulfonyl)-2-methyl-piperazine (H-7), and treatment of keratinocytes with 1,25-(OH)₂D₃ caused a rapid activation of protein kinase C and its translocation to the membranes. Formation of intercellular contacts may be an important mechanism of 1,25-(OH)₂D₃ action in hyperproliferative and neoplastic diseases.

This article has been cited by other articles:

				M. T. Mizwicki and A. W. Norman The Vitamin D Sterol-Vitamin D Receptor Ensemble Model Offers Unique Insights into Both Genomic and Rapid-Response Signaling Sci. Signal., June 16, 2009; 2(75): re4 - re4. [Abstract] [Full Text] [PDF]

				V. T. Nguyen, T. X. Lee, A. Ndoye, L. D. Shultz, M. R. Pittelkow, M. V. Dahl, P. J. Lynch, and S. A. Grando The Pathophysiological Significance of Nondesmoglein Targets of Pemphigus Autoimmunity: Development of Antibodies Against Keratinocyte Cholinergic Receptors in Patients With Pemphigus Vulgaris and Pemphigus Foliaceus Arch Dermatol, August 1, 1998; 134(8): 971 - 980. [Abstract] [Full Text] [PDF]

				H. G. Palmer, J. M. Gonzalez-Sancho, J. Espada, M. T. Berciano, I. Puig, J. Baulida, M. Quintanilla, A. Cano, A. G. de Herreros, M. Lafarga, et al. Vitamin D3 promotes the differentiation of colon carcinoma cells by the induction of E-cadherin and the inhibition of {beta}-catenin signaling J. Cell Biol., July 23, 2001; 154(2): 369 - 388. [Abstract] [Full Text] [PDF]