title: Differential expression of cell-cycle regulators in human beta-cells derived from insulinoma tissue.
abstract: BACKGROUND
  The low frequency of beta-cell replication in the adult human pancreas limits beta-cell regeneration. A better understanding of the regulation of human beta-cell proliferation is crucial to develop therapeutic strategies aiming to enhance beta-cell mass.
  
  
  METHODS
  To identify factors that control beta-cell proliferation, cell-cycle regulation was examined in human insulinomas as a model of increased beta-cell proliferation (n=11) and healthy pancreatic tissue from patients with benign pancreatic tumors (n=9). Tissue sections were co-stained for insulin and cell-cycle proteins. Transcript levels of selected cell-cycle factors in beta-cells were determined by qRT-PCR after performing laser-capture microdissection.
  
  
  RESULTS
  The frequency of beta-cell replication was 3.74±0.92% in the insulinomas and 0.11±0.04% in controls (p=0.0016). p21 expression was higher in insulinomas (p=0.0058), and Rb expression was higher by trend (p=0.085), whereas p16 (p<0.0001), Cyclin C (p<0.0001), and p57 (p=0.018) expression levels were lower. The abundance of Cyclin D3 (p=0.62) and p27 (p=0.68) was not different between the groups. The reduced expression of p16 (p<0.0001) and p57 (p=0.012) in insulinomas and the unchanged expression of Cyclin D3 (p=0.77) and p27 (p=0.55) were confirmed using qRT-PCR.
  
  
  CONCLUSIONS
  The expression of certain cell-cycle factors in beta-cells derived from insulinomas and healthy adults differs markedly. Targeting such differentially regulated cell-cycle proteins may evolve as a future strategy to enhance beta-cell regeneration.
authors.affiliation: Diabetes Division, St. Josef-Hospital, Ruhr-University Bochum, Gudrunstrasse 56, Bochum 44791, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Ueberberg
authors.affiliation: Department of Pathology, Ruhr-University Bochum, Bürkle de la Camp-Platz 1, Bochum 44789, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Tannapfel
authors.affiliation: Department of Surgery, Knappschaftskrankenhaus Bochum, Ruhr-University Bochum, In der Schornau 23-25, Bochum 44892, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Schenker
authors.affiliation: Department of Surgery, Knappschaftskrankenhaus Bochum, Ruhr-University Bochum, In der Schornau 23-25, Bochum 44892, Germany.
authors.forename: Richard
authors.initials: R
authors.lastname: Viebahn
authors.affiliation: Department of Surgery, St. Josef-Hospital, Ruhr-University Bochum, Gudrunstrasse 56, Bochum 44791, Germany.
authors.forename: Waldemar
authors.initials: W
authors.lastname: Uhl
authors.affiliation: Department of Medicine II, St. Vinzenz Hospital, Merheimer Str. 221-223, Cologne 50733, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Schneider
authors.affiliation: Diabetes Division, St. Josef-Hospital, Ruhr-University Bochum, Gudrunstrasse 56, Bochum 44791, Germany. Electronic address: Juris.meier@rub.de.
authors.forename: Juris J
authors.initials: JJ
authors.lastname: Meier
mesh_terms: D000236:Adenoma / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D000328:Adult; D000368:Aged; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D050417:Insulin-Secreting Cells / Q000378:metabolism* / Q000473:pathology; D007340:Insulinoma / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D061346:Laser Capture Microdissection; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D010179:Pancreas / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: D018797:Cell Cycle Proteins; D009363:Neoplasm Proteins
keywords: Beta-cell mass; Beta-cell proliferation; Diabetes; Ki67