Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 89-97 |
| Number of pages | 9 |
| Journal | Cancer Cell |
| Volume | 17 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Jan 19 2010 |
| Externally published | Yes |
Fingerprint
All Science Journal Classification (ASJC) codes
- Oncology
- Cell Biology
- Cancer Research
Cite this
Tobacco Smoke Promotes Lung Tumorigenesis by Triggering IKKβ- and JNK1-Dependent Inflammation. / Takahashi, Hiroyuki; Ogata, Hisanobu; Nishigaki, Reiko; Broide, David H.; Karin, Michael.
In: Cancer Cell, Vol. 17, No. 1, 19.01.2010, p. 89-97.Research output: Contribution to journal › Article
}
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
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.
UR - http://www.scopus.com/inward/record.url?scp=73649112422&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=73649112422&partnerID=8YFLogxK
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 -