TY - JOUR
T1 - Tobacco Smoke Promotes Lung Tumorigenesis by Triggering IKKβ- and JNK1-Dependent Inflammation
AU - Takahashi, Hiroyuki
AU - Ogata, Hisanobu
AU - Nishigaki, Reiko
AU - Broide, David H.
AU - Karin, Michael
N1 - Funding Information:
The authors thank Cell Signaling Technology for the gifts of antibodies. Research was supported by Grants from the National Institutes of Health, including the Superfund Research Program (P42ES010337 to M.K.) and Tobacco-Related Disease Research Program (15RT-0197 to M.K. and 12RT-0071 to D.H.B). H.T. and H.O. were supported by the Japanese Respiratory Society and Kanzawa Medical Research Foundation, respectively. M.K. is an American Cancer Society research professor.
PY - 2010/1/19
Y1 - 2010/1/19
N2 - Chronic exposure to tobacco smoke, which contains over 60 tumor-initiating carcinogens, is the major risk factor for development of lung cancer, accounting for a large portion of cancer-related deaths worldwide. It is well established that tobacco smoke is a tumor initiator, but we asked whether it also acts as a tumor promoter once malignant initiation, such as caused by K-ras activation, has taken place. Here we demonstrate that repetitive exposure to tobacco smoke promotes tumor development both in carcinogen-treated mice and in transgenic mice undergoing sporadic K-ras activation in lung epithelial cells. Tumor promotion is due to induction of inflammation that results in enhanced pneumocyte proliferation and is abrogated by IKKβ ablation in myeloid cells or inactivation of JNK1.
AB - Chronic exposure to tobacco smoke, which contains over 60 tumor-initiating carcinogens, is the major risk factor for development of lung cancer, accounting for a large portion of cancer-related deaths worldwide. It is well established that tobacco smoke is a tumor initiator, but we asked whether it also acts as a tumor promoter once malignant initiation, such as caused by K-ras activation, has taken place. Here we demonstrate that repetitive exposure to tobacco smoke promotes tumor development both in carcinogen-treated mice and in transgenic mice undergoing sporadic K-ras activation in lung epithelial cells. Tumor promotion is due to induction of inflammation that results in enhanced pneumocyte proliferation and is abrogated by IKKβ ablation in myeloid cells or inactivation of JNK1.
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U2 - 10.1016/j.ccr.2009.12.008
DO - 10.1016/j.ccr.2009.12.008
M3 - Article
C2 - 20129250
AN - SCOPUS:73649112422
VL - 17
SP - 89
EP - 97
JO - Cancer Cell
JF - Cancer Cell
SN - 1535-6108
IS - 1
ER -
