| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Carcinogenesis |
Departments of Pharmaceutical Sciences [L. R. K., B. S. B., L. D. D-N., B. B., D. C. T., A. M. M.] and Pharmacology [A. M. M.], University of Colorado Cancer Center, University of Colorado Health Sciences Center, Denver Colorado 80262, and Laboratory of Pulmonary Pathology, National Institute of Environmental Health Sciences, NIH, North Carolina 27709 [A. K. B.]
Inducible nitric oxide synthase (iNOS) content is elevated in human lung adenocarcinomas, and lung cancer patients exhale more nitric oxide (NO) than healthy individuals. The mechanism of this association of chronically elevated NO with tumorigenesis has not been defined. We investigated the role of iNOS in murine lung tumorigenesis, a model of human lung adenocarcinoma, using wild-type (+/+) and iNOS (-/-) mice. Genetic disruption of iNOS decreased urethane-induced lung tumor multiplicity by 80% (P < 0.0001). iNOS protein was expressed in lung tumors growing in wild-type mice and bronchiolar Clara cells isolated from normal mouse lungs, but was undetectable in whole lung extracts by immunoblotting. Because NO regulates vascular endothelial growth factor (VEGF) expression in other systems, we examined the effect of iNOS deficiency on VEGF protein concentration in mouse lung tumors. VEGF concentration was 54% lower in lung tumors isolated from iNOS (-/-) mice versus controls, implying that NO modulates angiogenesis in these tumors. Lung tumors also have elevated levels of cyclooxygenase (COX) -1 and COX-2 contents relative to normal lungs, but iNOS deficiency did not change COX expression in the tumors. Chronic inflammation predisposes mice to lung tumorigenesis; accordingly, we examined whether butylated hydroxytoluene-induced chronic lung inflammation was influenced by iNOS deficiency. Butylated hydroxytoluene-induced alveolar macrophage infiltration was unaffected by iNOS (-/-) status, suggesting that although NO is a critical mediator of mouse lung tumorigenesis, it is not essential in this model of lung inflammation. The substantial (80%) reduction in lung tumor multiplicity in iNOS (-/-) mice strongly supports examining iNOS-specific inhibitors as potential lung cancer chemopreventive agents.
This article has been cited by other articles:
|
|
 |
|
  A. K. Bauer and E. A. Rondini REVIEW PAPER: The Role of Inflammation in Mouse Pulmonary Neoplasia Vet. Pathol., May 1, 2009; 46(3): 369 - 390. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Tyagi, R. P. Singh, K. Ramasamy, K. Raina, E. F. Redente, L. D. Dwyer-Nield, R. A. Radcliffe, A. M. Malkinson, and R. Agarwal Growth Inhibition and Regression of Lung Tumors by Silibinin: Modulation of Angiogenesis by Macrophage-Associated Cytokines and Nuclear Factor-{kappa}B and Signal Transducers and Activators of Transcription 3 Cancer Prevention Research, January 1, 2009; 2(1): 74 - 83. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Jin, C.-X. Xu, H.-T. Lim, S.-J. Park, J.-Y. Shin, Y.-S. Chung, S.-C. Park, S.-H. Chang, H.-J. Youn, K.-H. Lee, et al. High Dietary Inorganic Phosphate Increases Lung Tumorigenesis and Alters Akt Signaling Am. J. Respir. Crit. Care Med., January 1, 2009; 179(1): 59 - 68. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Takahashi, T. Kitahashi, R. Ishigamori, M. Mutoh, M. Komiya, H. Sato, Y. Kamanaka, M. Naka, T. Maruyama, T. Sugimura, et al. Increased expression of inducible nitric oxide synthase (iNOS) in N-nitrosobis(2-oxopropyl)amine-induced hamster pancreatic carcinogenesis and prevention of cancer development by ONO-1714, an iNOS inhibitor Carcinogenesis, August 1, 2008; 29(8): 1608 - 1613. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.-X. Xu, D. Jere, H. Jin, S.-H. Chang, Y.-S. Chung, J.-Y. Shin, J.-E. Kim, S.-J. Park, Y.-H. Lee, C.-H. Chae, et al. Poly(ester amine)-mediated, Aerosol-delivered Akt1 Small Interfering RNA Suppresses Lung Tumorigenesis Am. J. Respir. Crit. Care Med., July 1, 2008; 178(1): 60 - 73. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Chittezhath, G. Deep, R. P. Singh, C. Agarwal, and R. Agarwal Silibinin inhibits cytokine-induced signaling cascades and down-regulates inducible nitric oxide synthase in human lung carcinoma A549 cells Mol. Cancer Ther., July 1, 2008; 7(7): 1817 - 1826. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. F. Gajewski, E. A. Grimm, B. J. Nickoloff, and A. T. Weeraratna New Potential Therapeutic Targets in Melanoma ASCO Educational Book, January 1, 2008; 2008(1): 404 - 407. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Guruvayoorappan and G. Kuttan {beta}-Carotene Inhibits Tumor-Specific Angiogenesis by Altering the Cytokine Profile and Inhibits the Nuclear Translocation of Transcription Factors in B16F-10 Melanoma Cells Integr Cancer Ther, September 1, 2007; 6(3): 258 - 270. [Abstract] [PDF]
|
|
|
|
 |
|
 E. F. Redente, D. J. Orlicky, R. J. Bouchard, and A. M. Malkinson Tumor Signaling to the Bone Marrow Changes the Phenotype of Monocytes and Pulmonary Macrophages during Urethane-Induced Primary Lung Tumorigenesis in A/J Mice Am. J. Pathol., February 1, 2007; 170(2): 693 - 708. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Pacher, J. S. Beckman, and L. Liaudet Nitric Oxide and Peroxynitrite in Health and Disease Physiol Rev, January 1, 2007; 87(1): 315 - 424. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. P. Singh, G. Deep, M. Chittezhath, M. Kaur, L. D. Dwyer-Nield, A. M. Malkinson, and R. Agarwal Effect of silibinin on the growth and progression of primary lung tumors in mice. J Natl Cancer Inst, June 21, 2006; 98(12): 846 - 855. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. D. Dwyer-Nield, M. C. Srebernak, B. S. Barrett, J. Ahn, P. Cosper, A. M. Meyer, L. R. Kisley, A. K. Bauer, D. C. Thompson, and A. M. Malkinson Cytokines differentially regulate the synthesis of prostanoid and nitric oxide mediators in tumorigenic versus non-tumorigenic mouse lung epithelial cell lines Carcinogenesis, July 1, 2005; 26(7): 1196 - 1206. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Chen, Y. Yan, J. Li, Q. Ma, G. D. Stoner, J. Ye, and C. Huang Differential requirement of signal pathways for benzo[a]pyrene (B[a]P)-induced nitric oxide synthase (iNOS) in rat esophageal epithelial cells Carcinogenesis, June 1, 2005; 26(6): 1035 - 1043. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Sugita, M. Fujimoto, T. Yasukawa, N. Shimizu, M. Sugita, S. Yasuhara, J. A. J. Martyn, and M. Kaneki Inducible Nitric-oxide Synthase and NO Donor Induce Insulin Receptor Substrate-1 Degradation in Skeletal Muscle Cells J. Biol. Chem., April 8, 2005; 280(14): 14203 - 14211. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. K. Bauer, A. M. Malkinson, and S. R. Kleeberger Susceptibility to neoplastic and non-neoplastic pulmonary diseases in mice: genetic similarities Am J Physiol Lung Cell Mol Physiol, October 1, 2004; 287(4): L685 - L703. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Meyer, L. D. Dwyer-Nield, G. J. Hurteau, R. L. Keith, E. O'Leary, M. You, J. V. Bonventre, R. A. Nemenoff, and A. M. Malkinson Decreased lung tumorigenesis in mice genetically deficient in cytosolic phospholipase A2 Carcinogenesis, August 1, 2004; 25(8): 1517 - 1524. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. R. Brown and R. N. DuBois Cyclooxygenase as a Target in Lung Cancer Clin. Cancer Res., June 15, 2004; 10(12): 4266S - 4269S. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. J. A. Fijneman, M. Vos, J. Berkhof, P. Demant, and G. Kraal Genetic Analysis of Macrophage Characteristics as a Tool to Identify Tumor Susceptibility Genes: Mapping of Three Macrophage-Associated Risk Inflammatory Factors, Marif1, Marif2, and Marif3 Cancer Res., May 15, 2004; 64(10): 3458 - 3464. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K.-S. Chun, H.-H. Cha, J.-W. Shin, H.-K. Na, K.-K. Park, W.-Y. Chung, and Y.-J. Surh Nitric oxide induces expression of cyclooxygenase-2 in mouse skin through activation of NF-{kappa}B Carcinogenesis, March 1, 2004; 25(3): 445 - 454. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Crowell, V. E. Steele, C. C. Sigman, and J. R. Fay Is Inducible Nitric Oxide Synthase a Target for Chemoprevention? Mol. Cancer Ther., August 1, 2003; 2(8): 815 - 823. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Dmitrovsky Combining Cytotoxic Chemotherapy With Cyclooxygenase-2 Inhibition J. Clin. Oncol., July 15, 2003; 21(14): 2631 - 2632. [Full Text] [PDF]
|
|
|
|
|
|
P. Klatt and M. Serrano Engineering cancer resistance in mice Carcinogenesis, May 1, 2003; 24(5): 817 - 826. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
