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

TitleDiminished expression of transcription factors nuclear factor kappaB and CCAAT/enhancer binding protein underlies a novel tumor evasion mechanism affecting macrophages of mammary tumor-bearing mice.
Publication TypeJournal Article
Year of Publication2005
AuthorsTorroella-Kouri M, Ma X, Perry G, Ivanova M, Cejas PJ, Owen JL, Iragavarapu-Charyulu V, Lopez DM
JournalCancer Res
Volume65
Issue22
Pagination10578-84
Date Published2005 Nov 15
ISSN0008-5472
KeywordsAnimals, CCAAT-Enhancer-Binding Proteins, Cell Nucleus, Female, I-kappa B Proteins, Interleukin-12, Macrophages, Peritoneal, Male, Mammary Neoplasms, Experimental, Mice, Mice, Inbred BALB C, NF-kappa B, NF-KappaB Inhibitor alpha, Phosphorylation, Promoter Regions, Genetic, RNA, Messenger
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 kappaB (NFkappaB) and CCAAT/enhancer binding protein (C/EBP) expression and function in tumor bearers' peritoneal macrophages. The constitutive expressions of NFkappaB p50, c-rel, p65, and C/EBPalpha and beta, as well as the lipopolysaccharide-induced nuclear translocation and DNA binding of NFkappaB components and C/EBPalpha and beta, 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.

DOI10.1158/0008-5472.CAN-05-0365
Alternate JournalCancer Res
PubMed ID16288051
PubMed Central IDPMC2963077
Grant ListR01 CA025583 / CA / NCI NIH HHS / United States
R01 CA100223 / CA / NCI NIH HHS / United States
R01 CA100223-01A1 / CA / NCI NIH HHS / United States
R01 CA25583 / CA / NCI NIH HHS / United States

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