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

被引:366
作者
Takahashi, Hiroyuki [1 ]
Ogata, Hisanobu [1 ]
Nishigaki, Reiko [1 ]
Broide, David H. [2 ]
Karin, Michael [1 ]
机构
[1] Univ Calif San Diego, Sch Med, Dept Pharmacol, Lab Gene Regulat & Signal Transduct, La Jolla, CA 92093 USA
[2] Univ Calif San Diego, Sch Med, Dept Med, La Jolla, CA 92093 USA
基金
美国国家卫生研究院;
关键词
NF-KAPPA-B; COLITIS-ASSOCIATED CANCER; CIGARETTE-SMOKE; A/J MOUSE; INNATE IMMUNITY; MICE; RAS; CELLS; CARCINOGENICITY; BIOCHEMISTRY;
D O I
10.1016/j.ccr.2009.12.008
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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 IKK beta ablation in myeloid cells or inactivation of JNK1.
引用
收藏
页码:89 / 97
页数:9
相关论文
共 37 条
  • [11] Biochemistry, biology, and carcinogenicity of tobacco-specific N-nitrosamines
    Hecht, SS
    [J]. CHEMICAL RESEARCH IN TOXICOLOGY, 1998, 11 (06) : 559 - 603
  • [12] Cigarette smoking and lung cancer: chemical mechanisms and approaches to prevention
    Hecht, SS
    [J]. LANCET ONCOLOGY, 2002, 3 (08) : 461 - 469
  • [13] Tobacco smoke carcinogens and lung cancer
    Hecht, SS
    [J]. JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, 1999, 91 (14): : 1194 - 1210
  • [14] Molecular origins of cancer: Lung cancer
    Herbst, Roy S.
    Heymach, John V.
    Lippman, Scott M.
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 2008, 359 (13) : 1367 - 1380
  • [15] Radical causes of cancer
    Hussain, SP
    Hofseth, LJ
    Harris, CC
    [J]. NATURE REVIEWS CANCER, 2003, 3 (04) : 276 - 285
  • [16] Resolution of airway inflammation following ovalbumin inhalation - Comparison of ISS DNA and corticosteroids
    Ikeda, RK
    Nayar, J
    Cho, JY
    Miller, M
    Rodriguez, M
    Raz, E
    Broide, DH
    [J]. AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 2003, 28 (06) : 655 - 663
  • [17] Cancer statistics, 2008
    Jemal, Ahmedin
    Siegel, Rebecca
    Ward, Elizabeth
    Hao, Yongping
    Xu, Jiaquan
    Murray, Taylor
    Thun, Michael J.
    [J]. CA-A CANCER JOURNAL FOR CLINICIANS, 2008, 58 (02) : 71 - 96
  • [18] K-ras activation generates an inflammatory response in lung tumors
    Ji, H
    Houghton, AM
    Mariani, TJ
    Perera, S
    Kim, CB
    Padera, R
    Tonon, G
    McNamara, K
    Marconcini, LA
    Hezel, A
    El-Bardeesy, N
    Bronson, RT
    Sugarbaker, D
    Maser, RS
    Shapiro, SD
    Wong, KK
    [J]. ONCOGENE, 2006, 25 (14) : 2105 - 2112
  • [19] Somatic activation of the K-ras oncogene causes early onset lung cancer in mice
    Johnson, L
    Mercer, K
    Greenbaum, D
    Bronson, RT
    Crowley, D
    Tuveson, DA
    Jacks, T
    [J]. NATURE, 2001, 410 (6832) : 1111 - 1116
  • [20] From JNK to pay dirt: Jun kinases, their biochemistry, physiology and clinical importance
    Karin, M
    Gallagher, E
    [J]. IUBMB LIFE, 2005, 57 (4-5) : 283 - 295