title: Expression patterns of protein kinase C isoenzymes are characteristically modulated in chronic pancreatitis and pancreatic cancer.
abstract: We immunohistochemically identified protein kinase C (PKC) isoenzymes and the receptor for activated C-kinase (RACK-1) in normal, chronically inflamed, and malignant pancreas specimens. Expression patterns were specific and consistent for each microanatomic structure. In chronic pancreatitis, the expression patterns by epithelial cells were indistinguishable from those in normal pancreas. In the stroma, there was a gain of PKC-delta (P < .05) and loss of PKC-mu (P < .0001). Expression in pancreatic duct carcinomas, compared with control normal minor ductular epithelial cells, revealed relative loss of PKC-epsilon (P < .0001), PKC-iota (P = .005), and PKC-theta (P < .0001) but no gain in any isoenzyme. Compared with control normal major duct epithelial cells, the principal differences were a relative loss in PKC-gamma (P < .05) and a relative gain in PKC-beta (P < .05), PKC-iota (P < .05), and PKC-zeta (P < .005). The stroma adjacent to ductal carcinomas was characterized by prominent expression of PKC-mu and a gain in PKC-delta (P < .0001) and PKC-zeta (P > .005). Ampullary carcinomas revealed a relative gain of PKC-iota (P < .05) and RACK-1 (P < .05). In the adjacent stroma was enhanced expression of PKC-delta (P < .005) and PKC-gamma (P < .001) and loss of PKC-mu (P < .05). Specific changes in isoenzyme expression in stroma of chronic pancreatitis and in epithelial cells and stroma of ductal and ampullary pancreatic adenocarcinomas reflect specific modulation of intracellular signaling pathways that control critical homeostatic mechanisms.
authors.affiliation: Department of Surgery, University of Liverpool, Daulby St., Liverpool L69 3GA, England.
authors.forename: James D
authors.initials: JD
authors.lastname: Evans
authors.forename: Philip A
authors.initials: PA
authors.lastname: Cornford
authors.forename: Andrew
authors.initials: A
authors.lastname: Dodson
authors.forename: John P
authors.initials: JP
authors.lastname: Neoptolemos
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Foster
mesh_terms: D021441:Carcinoma, Pancreatic Ductal / Q000201:enzymology* / Q000473:pathology; D002908:Chronic Disease; D006801:Humans; D007124:Immunoenzyme Techniques; D007527:Isoenzymes / Q000378:metabolism; D010179:Pancreas / Q000033:anatomy & histology / Q000201:enzymology / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000201:enzymology* / Q000473:pathology; D010195:Pancreatitis / Q000201:enzymology* / Q000473:pathology; D011493:Protein Kinase C / Q000145:classification / Q000378:metabolism*; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface / Q000378:metabolism
chemical_list: D007527:Isoenzymes; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface; D011493:Protein Kinase C