Interferon regulatory factor-1 (IRF-1) suppression and derepression during endometrial tumorigenesis and cancer progression

Cytokine. 2004 May 21;26(4):164-8. doi: 10.1016/j.cyto.2004.03.001.

Abstract

Interferon regulatory factor-1 (IRF-1) is a tumor suppressor gene presumed to be involved in the control of cellular proliferation and transformation. Given that the IRF-1 is consistently expressed in the normally cycling endometrium, the question was raised of the possible role of IRF-1 in the genesis of endometrial adenocarcinoma. A series of 25 normal and 86 malignant endometria was investigated using immunohistochemical techniques and the anti-IRF-1 polyclonal antibody c-20. Normal endometrial glands were, indeed, consistently reactive with IRF-1. Excluding the invading tumor front, malignant endometria were deprived of IRF-1 reactivity, as 81 of the 86 cases (94.2%) were negative for this antigen. At the invading tumor front, however, IRF-1 was derepressed in tumor cells in 35% of the cases. This phenomenon was independent of the extent of lymphocytic response, but it was associated with thymidine phosphorylase (TP) expression. Furthermore, TP up-regulation and host's lymphocytic response in the area were directly associated. IRF-1 derepression by invading tumor cells was associated with poor prognosis, independently of FIGO stage. It is concluded that down-regulation of IRF-1 is a constant finding in endometrial tumorigenesis. However, derepression of IRF-1 may occur in a subset of tumors, and this event is associated with TP up-regulation and aggressive tumor behavior.

MeSH terms

  • Adenocarcinoma / enzymology
  • Adenocarcinoma / etiology
  • Adenocarcinoma / metabolism
  • Cell Transformation, Neoplastic / metabolism*
  • DNA-Binding Proteins / metabolism*
  • Down-Regulation / physiology
  • Endometrial Neoplasms / enzymology
  • Endometrial Neoplasms / etiology*
  • Endometrial Neoplasms / metabolism
  • Female
  • Humans
  • Interferon Regulatory Factor-1
  • Multivariate Analysis
  • Phosphoproteins / metabolism*
  • Survival Analysis
  • Thymidine Phosphorylase / metabolism
  • Up-Regulation / physiology

Substances

  • DNA-Binding Proteins
  • IRF1 protein, human
  • Interferon Regulatory Factor-1
  • Phosphoproteins
  • Thymidine Phosphorylase