Diminished expression of transcription factors nuclear factor κB and CCAAT/enhancer binding protein underlies a novel tumor evasion mechanism affecting macrophages of mammary tumor-bearing mice

Marta Torroella-Kouri, Xiaojing Ma, Giselle Perry, Milena Ivanova, Pedro J. Cejas, Jennifer L. Owen, Vijaya Iragavarapu-Charyulu, Diana M Lopez

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Abstract

Interactions between malignant tumors and the host immune system shape the course of cancer progression. The molecular basis of such interactions is the subject of immense interest. Proinflammatory cytokines produced by macrophages are critical mediators of immune responses that contribute to the control of the advancement of neoplasia. We have shown that the expressions of interleukin 12 (IL-12) and inducible nitric oxide synthase (iNOS) are decreased in macrophages from mammary tumor-bearing mice. In this study, we investigated the causes of IL-12 dysregulation and found deficient nuclear factor κB (NFκB) and CCAAT/enhancer binding protein (C/EBP) expression and function in tumor bearers' peritoneal macrophages. The constitutive expressions of NFκB p50, c-rel, p65, and C/EBPα and β, as well as the lipopolysaccharide- induced nuclear translocation and DNA binding of NFκB components and C/EBPα and β, are profoundly impaired in macrophages from mice bearing D1-DMBA-3 tumors. Because similar findings occur with the iNOS gene, it seems that it represents a novel mechanism by which tumor-derived factors interfere with the host immune defenses.

Original languageEnglish
Pages (from-to)10578-10584
Number of pages7
JournalCancer Research
Volume65
Issue number22
DOIs
StatePublished - Nov 15 2005

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CCAAT-Enhancer-Binding Proteins
Transcription Factors
Macrophages
Breast Neoplasms
Neoplasms
Nitric Oxide Synthase Type II
Interleukin-12
9,10-Dimethyl-1,2-benzanthracene
Peritoneal Macrophages
Lipopolysaccharides
Immune System
Cytokines
DNA
Genes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Diminished expression of transcription factors nuclear factor κB and CCAAT/enhancer binding protein underlies a novel tumor evasion mechanism affecting macrophages of mammary tumor-bearing mice. / Torroella-Kouri, Marta; Ma, Xiaojing; Perry, Giselle; Ivanova, Milena; Cejas, Pedro J.; Owen, Jennifer L.; Iragavarapu-Charyulu, Vijaya; Lopez, Diana M.

In: Cancer Research, Vol. 65, No. 22, 15.11.2005, p. 10578-10584.

Research output: Contribution to journalArticle

Torroella-Kouri, Marta ; Ma, Xiaojing ; Perry, Giselle ; Ivanova, Milena ; Cejas, Pedro J. ; Owen, Jennifer L. ; Iragavarapu-Charyulu, Vijaya ; Lopez, Diana M. / Diminished expression of transcription factors nuclear factor κB and CCAAT/enhancer binding protein underlies a novel tumor evasion mechanism affecting macrophages of mammary tumor-bearing mice. In: Cancer Research. 2005 ; Vol. 65, No. 22. pp. 10578-10584.
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