Deficiency of C-C chemokine receptor 5 suppresses tumor development via inactivation of NF-κB and upregulation of IL-1Ra in melanoma model.
PLoS One
; 7(5): e33747, 2012.
Article
in En
| MEDLINE
| ID: mdl-22567084
ABSTRACT
To evaluate the relevance of C-C chemokine receptor type 5 (CCR5) expression and tumor development, we compared melanoma growth in CCR5 knockout (CCR5(-/-)) mice and wild type (CCR5(+/+)) mice. CCR5(-/-) mice showed reduced tumor volume, tumor weight, and increased survival rate when compared to CCR5(+/+) mice. We investigated the activation of NF-κB since it is an implicated transcription factor in the regulation of genes involving cell growth, apoptosis, and tumor growth. Significant inhibition of DNA binding activity of NF-κB, and translocation of p50 and p65 into the nucleus through the inhibition of phosphorylation of IκB was found in the melanoma tissues of CCR5(-/-) mice compared to melanoma tissues of CCR5(+/+) mice. NF-κB target apoptotic protein expression, such as cleaved caspase-3, cleaved PARP, and Bax, was elevated, whereas the survival protein expression levels, such as Bcl-2, C-IAP1, was decreased in the melanoma tissues of CCR5(-/-) mice. Interestingly, we found that the level of IL-1Ra, a tumor growth suppressive cytokine, was significantly elevated in tumor tissue and spleen of CCR5(-/-) mice compared to the level in CCR5(+/+) mice. Moreover, infiltration of CD8(+) cytotoxic T cell and CD57(+) natural killer cells was significantly increased in melanoma tumor and spleen tissue of CCR5(-/-) mice compared to that of CCR5(+/+) mice. Therefore, these results showed that CCR5 deficiency caused apoptotic cell death of melanoma through inhibition of NF-κB and upregulation of IL-1Ra.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
NF-kappa B
/
Receptors, CCR5
/
Interleukin 1 Receptor Antagonist Protein
/
Melanoma
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
PLoS One
Journal subject:
CIENCIA
/
MEDICINA
Year:
2012
Document type:
Article