PMID- 22907530
OWN - NLM
STAT- MEDLINE
DCOM- 20130308
LR  - 20141120
IS  - 1460-2180 (Electronic)
IS  - 0143-3334 (Linking)
VI  - 33
IP  - 12
DP  - 2012 Dec
TI  - Deficiency of C-C chemokine receptor 5 suppresses tumor development via 
      inactivation of NF-kappaB and inhibition of monocyte chemoattractant protein-1 in 
      urethane-induced lung tumor model.
PG  - 2520-8
LID - 10.1093/carcin/bgs265 [doi]
AB  - To evaluate the significance of C-C chemokine receptor type 5 (CCR5) in lung 
      tumor development, we compared carcinogen-induced tumor growth in CCR5 knockout 
      (CCR5(-/-)) mice and wild-type (CCR5(+/+)) mice. CCR5(-/-) mice showed reduced 
      urethane (1g/kg)-induced tumor incidence when compared with those of CCR5(+/+) 
      mice. We investigated the activation of nuclear factor-kappaB/STAT3 since these 
      are implicated transcription factors in the regulation of genes involving tumor 
      growth. Significant inhibition of DNA-binding activity of nuclear factor-kappaB 
      and STAT3, and the translocation of p50 and p65 into the nucleus and the 
      phosphorylation of IkB were found in the lungs of CCR5(-/-) mice compared with 
      the lungs of CCR5(+/+) mice. Expression of apoptotic protein such as cleaved 
      caspase-3, cleaved PARP and Bax was elevated, whereas the expression levels of 
      survival protein such as Bcl-2 and cIAP1 was decreased in the lungs of CCR5(-/-) 
      mice. Interestingly, we found that the level of monocyte chemoattractant 
      protein-1 (MCP-1), a tumor growth-promoting cytokine, was significantly reduced 
      in the lung tumor tissue and blood of CCR5(-/-) mice compared with the level in 
      CCR5(+/+) mice. In addition, CCR5 small interfering RNA (siRNA) and inhibitor of 
      MCP-1 blocked lung cancer cell growth, which was abolished by the addition of 
      MCP-1 protein in cultured lung cancer cells. Moreover, inactivation of CD8(+) 
      cytotoxic T cell and dendritic cells was significantly increased in the blood, 
      lung tumors and spleens of CCR5(-/-) mice compared with that of CCR5(+/+) mice. 
      Therefore, these results showed that CCR5 deficiency suppressed lung tumor 
      development through the inhibition of nuclear factor-kappaB/STAT3 pathways and 
      the downregulation of MCP-1 in the carcinogen-induced lung tumor model.
FAU - Lee, Nam Jin
AU  - Lee NJ
AD  - College of Pharmacy and Medical Research Center, Chungbuk National University, 
      Cheongju, 361-763, Korea.
FAU - Choi, Dong Young
AU  - Choi DY
FAU - Song, Ju Kyoung
AU  - Song JK
FAU - Jung, Yu Yeon
AU  - Jung YY
FAU - Kim, Dae Han
AU  - Kim DH
FAU - Kim, Tae Myung
AU  - Kim TM
FAU - Kim, Dae Joong
AU  - Kim DJ
FAU - Kwon, Sun Mi
AU  - Kwon SM
FAU - Kim, Kyung Bo
AU  - Kim KB
FAU - Choi, Kyung Eun
AU  - Choi KE
FAU - Moon, Dong Cheul
AU  - Moon DC
FAU - Kim, Youngsoo
AU  - Kim Y
FAU - Han, Sang Bae
AU  - Han SB
FAU - Hong, Jin Tae
AU  - Hong JT
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120820
PL  - England
TA  - Carcinogenesis
JT  - Carcinogenesis
JID - 8008055
RN  - 0 (CCR5 Receptor Antagonists)
RN  - 0 (Chemokine CCL2)
RN  - 0 (NF-kappa B)
RN  - 0 (Receptors, CCR5)
RN  - 0 (STAT3 Transcription Factor)
RN  - 3IN71E75Z5 (Urethane)
SB  - IM
MH  - Animals
MH  - Apoptosis
MH  - CCR5 Receptor Antagonists
MH  - CD8-Positive T-Lymphocytes/physiology
MH  - Chemokine CCL2/*antagonists & inhibitors
MH  - Dendritic Cells/physiology
MH  - Disease Models, Animal
MH  - Humans
MH  - Lung Neoplasms/chemically induced/pathology/*prevention & control
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - NF-kappa B/*antagonists & inhibitors/physiology
MH  - Receptors, CCR5/*physiology
MH  - STAT3 Transcription Factor/physiology
MH  - Urethane/toxicity
EDAT- 2012/08/22 06:00
MHDA- 2013/03/09 06:00
CRDT- 2012/08/22 06:00
PHST- 2012/08/22 06:00 [entrez]
PHST- 2012/08/22 06:00 [pubmed]
PHST- 2013/03/09 06:00 [medline]
AID - bgs265 [pii]
AID - 10.1093/carcin/bgs265 [doi]
PST - ppublish
SO  - Carcinogenesis. 2012 Dec;33(12):2520-8. doi: 10.1093/carcin/bgs265. Epub 2012 Aug 
      20.