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Induction of Mesenchymal-Epithelial Transitions in Sarcoma Cells
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Induction of Mesenchymal-Epithelial Transitions in Sarcoma Cells

Published on: April 7, 2017

Mutational and expressional analyses of NRF2 and KEAP1 in sarcomas

Eun Mi Je1, Chang Hyeok An, Nam Jin Yoo

  • 1Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul, Korea.

Tumori
|October 12, 2012
PubMed
Abstract

Insights

Nuclear factor erythroid 2-related factor 2 (NRF2) and KEAP1 gene alterations are investigated in human sarcomas. While no gene mutations were found, NRF2 and GCLC expression was high, and KEAP1 expression was lost in some sarcomas, suggesting NRF2 pathway activation.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • The Nuclear factor erythroid 2-related factor 2 (NRF2) pathway regulates cytoprotective proteins, enhancing cancer cell survival.
  • KEAP1 normally inhibits NRF2 by mediating its degradation.
  • Somatic mutations in NRF2 and KEAP1 genes and loss of KEAP1 expression are implicated in various carcinomas.

Purpose of the Study:

  • To investigate whether mutational and expressional alterations of NRF2 and KEAP1 genes are characteristic of human sarcomas.
  • To assess the potential role of the NRF2/KEAP1 system in sarcoma development and progression.

Main Methods:

  • Somatic mutations of NRF2 and KEAP1 genes were analyzed in 108 sarcoma tissues using single-strand conformation polymorphism.
  • Immunohistochemistry was employed to analyze the expression of NRF2, KEAP1, and GCLC in sarcoma tissues.
  • The study included diverse sarcoma subtypes such as malignant fibrous histiocytomas, rhabdomyosarcomas, and osteosarcomas.

Main Results:

  • NRF2 and GCLC were expressed in 93% and 76% of sarcomas, respectively, indicating potential NRF2 pathway activation.
  • Loss of KEAP1 expression was observed in 24% of the sarcomas analyzed.
  • No somatic gene mutations were detected in either the NRF2 or KEAP1 genes within the studied sarcoma cohort.

Conclusions:

  • The findings suggest a possible activation of the NRF2/KEAP1 system in human sarcomas.
  • This activation may contribute to the cytoprotection of sarcoma cells, potentially influencing tumor survival and resistance.

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