title: E-cadherin interactions regulate beta-cell proliferation in islet-like structures.
abstract: Islet function is dependent on cells within the islet interacting with each other. E-cadherin (ECAD) mediates Ca(2+)-dependent homophilic cell adhesion between b-cells within islets and has been identified as a tumour suppressor. We generated clones of the MIN6 beta-cell line that stably over- (S) and under-express (alphaS) ECAD. Modified expression of ECAD was confirmed by quantitative RT-PCR, immunoblotting and immunocytochemistry. Preproinsulin mRNA, insulin content and basal rates of insulin secretion were higher in S cells compared to aS and control (V) cells. However, stimulated insulin secretory responses were unaffected by ECAD expression levels. ECAD expression did affect proliferation, with enhanced ECAD expression being associated with reduced proliferation and vice versa. Formation of islet-like structures was associated with a significant reduction in proliferation of V and S cells but not alphaS cells. These data suggest that ECAD expression levels do not modulate insulin secretory function but are consistent with a role for ECAD in the regulation of beta-cell proliferation.
authors.affiliation: Beta Cell Development and Function Group, School of Biomedical and Health Sciences, King's College London, London, UK. Melanie.Carvell@kcl.ac.uk
authors.forename: Melanie J
authors.initials: MJ
authors.lastname: Carvell
authors.forename: Phil J
authors.initials: PJ
authors.lastname: Marsh
authors.forename: Shanta J
authors.initials: SJ
authors.lastname: Persaud
authors.forename: Peter M
authors.initials: PM
authors.lastname: Jones
mesh_terms: D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D051177:Catenins / Q000378:metabolism; D002460:Cell Line; D049109:Cell Proliferation; D005786:Gene Expression Regulation; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000166:cytology* / Q000378:metabolism*; D011485:Protein Binding
chemical_list: D015820:Cadherins; D051177:Catenins; D007328:Insulin