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This Article Full Text Full Text (PDF) All Versions of this Article: 288/3/E502    most recent 00424.2004v1 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 Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Web of Science (8) Citing Articles via Google Scholar Google Scholar Articles by Luther, M. J. Articles by Jones, P. M. Search for Related Content PubMed PubMed Citation Articles by Luther, M. J. Articles by Jones, P. M.

Cell-to-cell contact influences proliferative marker expression and apoptosis in MIN6 cells grown in islet-like structures

¹-Cell Development and Function Group, Division of Reproductive Health, Endocrinology and Development, King's College London, Guy's Campus, London Bridge, London; and ²School of Pharmacy and Biomolecular Sciences, University of Brighton, Brighton, United Kingdom

Submitted 6 September 2004 ; accepted in final form 9 October 2004

Cell-to-cell interactions play an important role in the development and maintenance of the -cell phenotype. Here, we have investigated whether E-cadherin plays a role in regulating the growth of insulin-secreting MIN6 cells configured as three-dimensional islet-like clusters (pseudoislets). Pseudoislets form by cell aggregation rather than by proliferation from individual cells and attain the size of primary mouse islets after 7 days of maintenance in culture. E-cadherin is known to mediate homotypic cell adhesion between -cells and has also been implicated in a number of cellular processes, including proliferation, apoptosis, and differentiation. E-cadherin and its associated intracellular elements, - and -catenin, were upregulated in MIN6 pseudoislets. Pseudoislet formation was associated with an increased expression of cyclin-dependent kinase inhibitors and a concomitant downregulation of Ki67, suggesting an overall reduction in cellular proliferation. However, measurements of 5-bromo-2'-deoxyuridine incorporation revealed that there were no differences in the rate of MIN6 cell proliferation whether they were configured as monolayers or as pseudoislets, which is likely to be a result of their being a transformed cell line. Cells within pseudoislets were not necrotic, but apoptosis appeared to be upregulated in the islet-like structures. However, no differential expression of Fas and FasL was detected in monolayers and pseudoislets. These results suggest that cell-to-cell interactions within islet-like structures may initiate antiproliferative and proapoptotic signals.

islets of Langerhans; cell adhesion; E-cadherin; proliferation; pseudoislets