title: Serum deprivation induces glucose response and intercellular coupling in human pancreatic adenocarcinoma PANC-1 cells.
abstract: OBJECTIVE
  This study aimed to investigate whether the previously described differentiating islet-like aggregates of human pancreatic adenocarcinoma cells (PANC-1) develop glucose response and exhibit intercellular communication.
  
  
  METHODS
  Fura 2-loaded PANC-1 cells in serum-free medium were assayed for changes in cytosolic free calcium ([Ca]i) induced by depolarization, tolbutamide inhibition of K(ATP) channels, or glucose. Dye transfer, assayed by confocal microscopy or by FACS, was used to detect intercellular communication. Changes in messenger RNA (mRNA) expression of genes of interest were assessed by quantitative real-time polymerase chain reaction. Proliferation was assayed by the MTT method.
  
  
  RESULTS
  Serum-deprived PANC-1 cell aggregates developed [Ca]i response to KCl, tolbutamide, or glucose. These responses were accompanied by 5-fold increase in glucokinase mRNA level and, to a lesser extent, of mRNAs for K(ATP) and L-type calcium channels, as well as increase in mRNA levels of glucagon and somatostatin. Trypsin, a proteinase-activated receptor 2 agonist previously shown to enhance aggregation, modestly improved [Ca]i response to glucose. Glucose-induced coordinated [Ca]i oscillations and dye transfer demonstrated the emergence of intercellular communication.
  
  
  CONCLUSIONS
  These findings suggest that PANC-1 cells, a pancreatic adenocarcinoma cell line, can be induced to express a differentiated phenotype in which cells exhibit response to glucose and form a functional syncytium similar to those observed in pancreatic islets.
authors: Department of Physiology and Pharmacology, Tel Aviv University, Ramat Aviv, Israel.
authors: Sahar
authors: S
authors: Hiram-Bab
authors: Yuval
authors: Y
authors: Shapira
authors: Marvin C
authors: MC
authors: Gershengorn
authors: Yoram
authors: Y
authors: Oron
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002118:Calcium / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D020013:Calcium Signaling; D002450:Cell Communication / Q000187:drug effects; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002469:Cell Separation / Q000379:methods; D016895:Culture Media, Serum-Free; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D054086:KATP Channels / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D008564:Membrane Potentials; D018613:Microscopy, Confocal; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D010641:Phenotype; D026902:Potassium Channel Blockers / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D014044:Tolbutamide / Q000494:pharmacology; D014357:Trypsin / Q000494:pharmacology
chemical_list: D020746:Calcium Channels, L-Type; D016895:Culture Media, Serum-Free; D054086:KATP Channels; D026902:Potassium Channel Blockers; D012333:RNA, Messenger; D014044:Tolbutamide; D014357:Trypsin; D005947:Glucose; D002118:Calcium