Tobacco Smoke Promotes Lung Tumorigenesis by Triggering IKKβ- and JNK1-Dependent Inflammation

Hiroyuki Takahashi, Hisanobu Ogata, Reiko Nishigaki, David H. Broide, Michael Karin

Research output: Contribution to journalArticle

257 Citations (Scopus)

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 languageEnglish
Pages (from-to)89-97
Number of pages9
JournalCancer Cell
Volume17
Issue number1
DOIs
Publication statusPublished - Jan 19 2010
Externally publishedYes

Fingerprint

Smoke
Carcinogens
Tobacco
Carcinogenesis
Inflammation
Lung
Neoplasms
Alveolar Epithelial Cells
Myeloid Cells
Transgenic Mice
Lung Neoplasms
Epithelial Cells

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 journalArticle

Takahashi, Hiroyuki ; Ogata, Hisanobu ; Nishigaki, Reiko ; Broide, David H. ; Karin, Michael. / Tobacco Smoke Promotes Lung Tumorigenesis by Triggering IKKβ- and JNK1-Dependent Inflammation. In: Cancer Cell. 2010 ; Vol. 17, No. 1. pp. 89-97.
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