| First Author | Song JK | Year | 2012 |
| Journal | PLoS One | Volume | 7 |
| Issue | 5 | Pages | e33747 |
| PubMed ID | 22567084 | Mgi Jnum | J:187266 |
| Mgi Id | MGI:5435996 | Doi | 10.1371/journal.pone.0033747 |
| Citation | Song JK, et al. (2012) Deficiency of C-C chemokine receptor 5 suppresses tumor development via inactivation of NF-kappaB and upregulation of IL-1Ra in melanoma model. PLoS One 7(5):e33747 |
| abstractText | 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-kappaB 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-kappaB, and translocation of p50 and p65 into the nucleus through the inhibition of phosphorylation of IkappaB was found in the melanoma tissues of CCR5(-/-) mice compared to melanoma tissues of CCR5(+/+) mice. NF-kappaB 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-kappaB and upregulation of IL-1Ra. |
