title: The roles of interferon regulatory factors 1 and 2 in the progression of human pancreatic cancer.
abstract: OBJECTIVE
  Pancreatic cancer is one of the most malignant diseases worldwide. Interferon regulatory factor (IRF) 1 and IRF2 function as a tumor suppressor and oncoprotein, respectively, in several types of cancers. We investigated whether IRF1 and IRF2 are involved in the progression of pancreatic cancer.
  
  
  METHODS
  We examined the expressions of IRF1 and IRF2 in pancreatic cancer specimens and analyzed the association with clinicopathologic features. We evaluated the biological effects of IRF1 and IRF2 using a pancreatic cancer cell line.
  
  
  RESULTS
  The expression levels of IRF1 and IRF2 were decreased and increased, respectively, in the pancreatic cancer cells compared with those observed in the paired normal areas. A higher expression of IRF1 was associated with better features of tumor differentiation, infiltration depth, tumor size, and survival, whereas that of IRF2 was associated with a worse feature of tumor infiltration depth. Interferon regulatory factor 2-overexpressing PANC-1 cells exhibited an increase in cell growth, less apoptotic features, and chemoresistance to gemcitabine treatment. In contrast, IRF1-overexpressing cells exhibited the opposite characteristics.
  
  
  CONCLUSIONS
  Interferon regulatory factors 1 and 2 may regulate the progression of pancreatic cancer by functioning as an antioncoprotein and oncoprotein, respectively. These molecules may serve as potential targets of therapy.
authors.affiliation: From the Departments of *Gastroenterology and †Gastroenterological Surgery, Akita University Graduate School of Medicine, Akita, Japan.
authors.forename: Toshitaka
authors.initials: T
authors.lastname: Sakai
authors.forename: Hirosato
authors.initials: H
authors.lastname: Mashima
authors.forename: Yumi
authors.initials: Y
authors.lastname: Yamada
authors.forename: Takashi
authors.initials: T
authors.lastname: Goto
authors.forename: Wataru
authors.initials: W
authors.lastname: Sato
authors.forename: Takahiro
authors.initials: T
authors.lastname: Dohmen
authors.forename: Kentaro
authors.initials: K
authors.lastname: Kamada
authors.forename: Masato
authors.initials: M
authors.lastname: Yoshioka
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Uchinami
authors.forename: Yuzo
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Hirohide
authors.initials: H
authors.lastname: Ohnishi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000494:pharmacology; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D050856:Interferon Regulatory Factor-1 / Q000235:genetics / Q000378:metabolism*; D050836:Interferon Regulatory Factor-2 / Q000235:genetics / Q000378:metabolism*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; C494257:IRF1 protein, human; C494229:IRF2 protein, human; D050856:Interferon Regulatory Factor-1; D050836:Interferon Regulatory Factor-2; D003841:Deoxycytidine; D000093542:Gemcitabine