title: Clinicopathological significance and molecular regulation of maspin expression in ductal adenocarcinoma of the pancreas.
abstract: We evaluated the biological relevance of maspin expression in pancreatic ductal adenocarcinoma and studied regulatory mechanisms of maspin gene activation in pancreatic carcinoma cell lines. Maspin expression was immunohistochemically detected in a series of 57 pancreatic ductal adenocarcinomas, 51 (90%) of which were classified as high-expressers. In lymph node metastases, maspin expression was somewhat decreasingly found in 39/49 (80%). Maspin high-expressers showed predominantly a low histological grade (p=0.013). Moreover, maspin expression was found in two mixed ductal-endocrine carcinomas, but not in 10 endocrine tumors and the surrounding normal pancreatic tissues. Using a luciferase reporter system, maspin promoter activity was induced in the maspin-positive pancreatic cancer cell lines as well as maspin-negative PANC-1 cells. Additionally, treatment with the DNA methyltransferase inhibitor, 5-aza-2' deoxycytidine, and histone deacetylase inhibitor, trichostatin A, led to re-expression of maspin mRNA in PANC-1 cells. Our results indicate that maspin expression is up-regulated in most if not all pancreatic ductal adenocarcinomas and may be related to the development and differentiation, and that DNA methylation and histone deacetylation may suppress maspin gene activation in pancreatic cancer cells.
authors.affiliation: Department of Pathology, University of Kiel, Kiel, Germany.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Ohike
authors.forename: Nicolai
authors.initials: N
authors.lastname: Maass
authors.forename: Christoph
authors.initials: C
authors.lastname: Mundhenke
authors.forename: Marco
authors.initials: M
authors.lastname: Biallek
authors.forename: Ming
authors.initials: M
authors.lastname: Zhang
authors.forename: Walter
authors.initials: W
authors.lastname: Jonat
authors.forename: Jutta
authors.initials: J
authors.lastname: Lüttges
authors.forename: Toshio
authors.initials: T
authors.lastname: Morohoshi
authors.forename: Günter
authors.initials: G
authors.lastname: Klöppel
authors.forename: Koichi
authors.initials: K
authors.lastname: Nagasaki
mesh_terms: D000107:Acetylation; D000368:Aged; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000037:antagonists & inhibitors; D000077209:Decitabine; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D020868:Gene Silencing; D016147:Genes, Tumor Suppressor; D056572:Histone Deacetylase Inhibitors; D006657:Histones / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D007124:Immunoenzyme Techniques; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011401:Promoter Regions, Genetic / Q000235:genetics; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D015843:Serpins / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
chemical_list: D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D006877:Hydroxamic Acids; D011506:Proteins; C085344:SERPIN-B5; D015843:Serpins; C012589:trichostatin A; D000077209:Decitabine; D015254:DNA Modification Methylases; D001374:Azacitidine