Role of the proteasome in the downregulation of transcription factors NFκB and C/EBP in macrophages from tumor hosts

  • Authors:
    • Giselle Perry
    • Viyaya Iragavarapu-Charyulu
    • Edward W. Harhaj
    • Marta Torroella-Kouri
  • View Affiliations

  • Published online on: March 1, 2010     https://doi.org/10.3892/or_00000710
  • Pages: 875-881
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Macrophages from mice bearing advanced mammary tumors are critically impaired in their immune functions, exhibiting reduced expression at the mRNA and protein levels of the crucial transcription factors, nuclear factor κB (NFκB) and CCAAT enhancer binding protein (C/EBP). We have previously shown that tumor-derived factors such as transforming growth factor β (TGFβ) and prostaglandin E2 (PGE2) modulate NFκB and C/EBP expression in macrophages. Transcriptional, post-transcriptional, translational and/or post-translational mechanisms may also play a role in altered levels of NFκB and C/EBP in macrophages from tumor hosts, contributing to impaired inflammatory response. One of the post-translational mechanisms that may tune down or recycle proteins in cells is the proteasomal pathway. Since upregulation of ubiquitin/proteasomal pathways has been described under cancer-induced cachexia, we examined the possible role of this proteolytic machinery in the decrease of NFκB and C/EBP proteins in macrophages from tumor hosts. Using MG-132 proteasome inhibitor to block the proteasome machinery in macrophages from normal and tumor-bearing animals we found that macrophages from tumor hosts display higher ubiquitination and proteolysis compared to those from normal mice and also that NFκB and C/EBP downregulation is reversed in these treated cells. Thus, proteasome degradation may contribute, at least in part, to NFκB and C/EBP impairment in macrophages from tumor-bearers.

Related Articles

Journal Cover

March 2010
Volume 23 Issue 3

Print ISSN: 1021-335X
Online ISSN:1791-2431

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Perry G, Iragavarapu-Charyulu V, Harhaj EW and Torroella-Kouri M: Role of the proteasome in the downregulation of transcription factors NFκB and C/EBP in macrophages from tumor hosts. Oncol Rep 23: 875-881, 2010
APA
Perry, G., Iragavarapu-Charyulu, V., Harhaj, E.W., & Torroella-Kouri, M. (2010). Role of the proteasome in the downregulation of transcription factors NFκB and C/EBP in macrophages from tumor hosts. Oncology Reports, 23, 875-881. https://doi.org/10.3892/or_00000710
MLA
Perry, G., Iragavarapu-Charyulu, V., Harhaj, E. W., Torroella-Kouri, M."Role of the proteasome in the downregulation of transcription factors NFκB and C/EBP in macrophages from tumor hosts". Oncology Reports 23.3 (2010): 875-881.
Chicago
Perry, G., Iragavarapu-Charyulu, V., Harhaj, E. W., Torroella-Kouri, M."Role of the proteasome in the downregulation of transcription factors NFκB and C/EBP in macrophages from tumor hosts". Oncology Reports 23, no. 3 (2010): 875-881. https://doi.org/10.3892/or_00000710