The roles of interferon regulatory factors 1 and 2 in the progression of human pancreatic cancer

Pancreas. 2014 Aug;43(6):909-16. doi: 10.1097/MPA.0000000000000116.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antimetabolites, Antineoplastic / pharmacology
  • Apoptosis / drug effects
  • Caco-2 Cells
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Deoxycytidine / analogs & derivatives
  • Deoxycytidine / pharmacology
  • Disease Progression
  • Female
  • Gemcitabine
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunohistochemistry
  • Interferon Regulatory Factor-1 / genetics
  • Interferon Regulatory Factor-1 / metabolism*
  • Interferon Regulatory Factor-2 / genetics
  • Interferon Regulatory Factor-2 / metabolism*
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Mutation
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / metabolism*
  • Pancreatic Neoplasms / pathology
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Antimetabolites, Antineoplastic
  • IRF1 protein, human
  • IRF2 protein, human
  • Interferon Regulatory Factor-1
  • Interferon Regulatory Factor-2
  • Deoxycytidine
  • Gemcitabine