Pancreatic tumoral cell line AR42J: an amphicrine model.
AR42J cells derive from azaserine-induced malignant nodules from the rat pancreas. They differ from normal acinar cells for at least three reasons: 1) they proliferate rapidly; 2) they synthesize, store, and secrete digestive enzymes but the regulation of their exocrine function is abnormal, from the emergence of atypical receptors (e.g., cholecystokinin octapeptide type B and pituitary adenylate cyclase-activating polypeptide type I receptors) to unusual inositol phosphate metabolism and cytoskeleton disorganization; and 3) they possess an added neuroendocrine-regulated pathway characterized by voltage-sensitive ionic currents, post-translational processing of peptidic prohormones (and possibly autocriny), and the release of small neurotransmitters (gamma-aminobutyric acid, glycine, and glutamic acid). These amphicrine cells represent, therefore, a cancerous version of the primordial pancreatic ductular epithelium. Dexamethasone favors their differentiation toward the exocrine phenotype. The mitogenic pathway is favored by the occupancy of receptor tyrosine kinases, adenosine 3',5'-cyclic monophosphate, ornithine decarboxylase expression, and Na(+)-H+ exchange. Somatostatin opposes proliferation through protein phosphatases.
Christophe
J
J
Department of Biochemistry and Nutrition, Medical School, Université Libre de Bruxelles, Belgium.
D000818:Animals; D002454:Cell Differentiation; D003907:Dexamethasone / Q000494:pharmacology; D004063:Digestion; D004798:Enzymes / Q000378:metabolism; D005089:Exocytosis; D019204:GTP-Binding Proteins / Q000502:physiology; D006801:Humans; D007473:Ion Channels / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D011949:Receptors, Cholecystokinin / Q000378:metabolism; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
D004798:Enzymes; D007473:Ion Channels; D011949:Receptors, Cholecystokinin; D003907:Dexamethasone; D019204:GTP-Binding Proteins