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Cancer Prevention pp 135–153Cite as

The Use of Mouse Models for Lung Cancer Chemoprevention Studies

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Part of the book series: Methods in Pharmacology and Toxicology ((MIPT))

Abstract

Mouse lung tumor models are widely used in lung cancer chemopreventive studies. Lung cancer is a heterogeneous disease histologically classified as small-cell lung carcinoma (SCLC) and non-small-cell lung carcinoma (NSCLC), which is usually divided into adenocarcinoma, squamous cell carcinoma (SCC), and large cell carcinoma. In order to illustrate the power of the mouse model in preclinical lung cancer investigations, comprehensive instructions for the selection of mice, genotyping, and induction of lung tumors (e.g., adenoma/adenocarcinoma, lung SCC, and SCLC) in mice are provided. We have described in detail the histological features of these tumors and the application of these features in lung cancer chemoprevention studies. We have also provided detailed information on how to semiquantitatively phenotype lung tumor development. The basic protocol described here could easily be applied to other approaches to lung cancer prevention such as chemoprevention or immunoprevention.

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References

  1. Siegel R, Naishadham D, Jemal A (2013) Cancer statistics, 2013. CA Cancer J Clin 63(1):11–30. doi:10.3322/caac.21166

    Article  PubMed  Google Scholar 

  2. Doll R, Hill AB (1952) A study of the aetiology of carcinoma of the lung. Br Med J 2(4797):1271–1286

    Article  PubMed  CAS  Google Scholar 

  3. Herzog CR, Lubet RA, You M (1997) Genetic alterations in mouse lung tumors: implications for cancer chemoprevention. J Cell Biochem Suppl 28–29:49–63

    Article  PubMed  Google Scholar 

  4. Shopland DR, Eyre HJ, Pechacek TF (1991) Smoking-attributable cancer mortality in 1991: is lung cancer now the leading cause of death among smokers in the United States? J Natl Cancer Inst 83(16):1142–1148

    Article  PubMed  CAS  Google Scholar 

  5. Minna JD (1993) The molecular biology of lung cancer pathogenesis. Chest 103(4 Suppl):449S–456S

    Article  PubMed  CAS  Google Scholar 

  6. Jemal A, Siegel R, Xu J, Ward E (2010) Cancer statistics, 2010. CA Cancer J Clin 60(5):277–300. doi:10.3322/caac.20073

    Article  PubMed  Google Scholar 

  7. Herbst RS, Heymach JV, Lippman SM (2008) Lung cancer. N Engl J Med 359(13):1367–1380. doi:10.1056/NEJMra0802714

    Article  PubMed  CAS  Google Scholar 

  8. Goldstraw P, Crowley J, Chansky K, Giroux DJ, Groome PA, Rami-Porta R, Postmus PE, Rusch V, Sobin L (2007) The IASLC Lung Cancer Staging Project: proposals for the revision of the TNM stage groupings in the forthcoming (seventh) edition of the TNM Classification of malignant tumours. J Thorac Oncol 2(8):706–714. doi:10.1097/JTO.0b013e31812f3c1a

    Article  PubMed  Google Scholar 

  9. Mountain CF, Dresler CM (1997) Regional lymph node classification for lung cancer staging. Chest 111(6):1718–1723

    Article  PubMed  CAS  Google Scholar 

  10. Mountain CF (1997) Revisions in the international system for staging lung cancer. Chest 111(6):1710–1717

    Article  PubMed  CAS  Google Scholar 

  11. Alifano M, Souaze F, Dupouy S, Camilleri-Broet S, Younes M, Ahmed-Zaid SM, Takahashi T, Cancellieri A, Damiani S, Boaron M, Broet P, Miller LD, Gespach C, Regnard JF, Forgez P (2010) Neurotensin receptor 1 determines the outcome of non-small cell lung cancer. Clin Cancer Res 16(17):4401–4410. doi:10.1158/1078-0432.CCR-10-0659

    Article  PubMed  CAS  Google Scholar 

  12. Lovly CM, Carbone DP (2011) Lung cancer in 2010: one size does not fit all. Nat Rev Clin Oncol 8(2):68–70. doi:10.1038/nrclinonc.2010.224

    Article  PubMed  CAS  Google Scholar 

  13. (2012) Comprehensive genomic characterization of squamous cell lung cancers. Nature 489(7417):519–525. doi:10.1038/nature11404

  14. Lockwood WW, Wilson IM, Coe BP, Chari R, Pikor LA, Thu KL, Solis LM, Nunez MI, Behrens C, Yee J, English J, Murray N, Tsao MS, Minna JD, Gazdar AF, Wistuba II, MacAulay CE, Lam S, Lam WL (2012) Divergent genomic and epigenomic landscapes of lung cancer subtypes underscore the selection of different oncogenic pathways during tumor development. PLoS One 7(5):e37775. doi:10.1371/journal.pone.0037775

    Article  PubMed  CAS  Google Scholar 

  15. Hainsworth JD, Cebotaru CL, Kanarev V, Ciuleanu TE, Damyanov D, Stella P, Ganchev H, Pover G, Morris C, Tzekova V (2010) A phase II, open-label, randomized study to assess the efficacy and safety of AZD6244 (ARRY-142886) versus pemetrexed in patients with non-small cell lung cancer who have failed one or two prior chemotherapeutic regimens. J Thorac Oncol 5(10):1630–1636. doi:10.1097/JTO.0b013e3181e8b3a3

    Article  PubMed  Google Scholar 

  16. Huynh H, Soo KC, Chow PK, Tran E (2007) Targeted inhibition of the extracellular signal-regulated kinase kinase pathway with AZD6244 (ARRY-142886) in the treatment of hepatocellular carcinoma. Mol Cancer Ther 6(1):138–146. doi:10.1158/1535-7163.MCT-06-0436

    Article  PubMed  CAS  Google Scholar 

  17. Ball DW, Jin N, Rosen DM, Dackiw A, Sidransky D, Xing M, Nelkin BD (2007) Selective growth inhibition in BRAF mutant thyroid cancer by the mitogen-activated protein kinase kinase 1/2 inhibitor AZD6244. J Clin Endocrinol Metab 92(12):4712–4718. doi:10.1210/jc.2007-1184

    Article  PubMed  CAS  Google Scholar 

  18. Haass NK, Sproesser K, Nguyen TK, Contractor R, Medina CA, Nathanson KL, Herlyn M, Smalley KS (2008) The mitogen-activated protein/extracellular signal-regulated kinase kinase inhibitor AZD6244 (ARRY-142886) induces growth arrest in melanoma cells and tumor regression when combined with docetaxel. Clin Cancer Res 14(1):230–239. doi:10.1158/1078-0432.CCR-07-1440

    Article  PubMed  CAS  Google Scholar 

  19. Ammoun S, Ristic N, Matthies C, Hilton DA, Hanemann CO (2010) Targeting ERK1/2 activation and proliferation in human primary schwannoma cells with MEK1/2 inhibitor AZD6244. Neurobiol Dis 37(1):141–146. doi:10.1016/j.nbd.2009.09.017

    Article  PubMed  CAS  Google Scholar 

  20. Estensen RD, Wattenberg LW (1993) Studies of chemopreventive effects of myo-inositol on benzo[a]pyrene-induced neoplasia of the lung and forestomach of female A/J mice. Carcinogenesis 14(9):1975–1977

    Article  PubMed  CAS  Google Scholar 

  21. Wattenberg LW, Wiedmann TS, Estensen RD, Zimmerman CL, Steele VE, Kelloff GJ (1997) Chemoprevention of pulmonary carcinogenesis by aerosolized budesonide in female A/J mice. Cancer Res 57(24):5489–5492

    PubMed  CAS  Google Scholar 

  22. Wang Y, Zhang Z, Kastens E, Lubet RA, You M (2003) Mice with alterations in both p53 and Ink4a/Arf display a striking increase in lung tumor multiplicity and progression: differential chemopreventive effect of budesonide in wild-type and mutant A/J mice. Cancer Res 63(15):4389–4395

    PubMed  CAS  Google Scholar 

  23. Zhang Z, Liu Q, Lantry LE, Wang Y, Kelloff GJ, Anderson MW, Wiseman RW, Lubet RA, You M (2000) A germ-line p53 mutation accelerates pulmonary tumorigenesis: p53-independent efficacy of chemopreventive agents green tea or dexamethasone/myo-inositol and chemotherapeutic agents taxol or adriamycin. Cancer Res 60(4):901–907

    PubMed  CAS  Google Scholar 

  24. Anderson MW, Goodin C, Zhang Y, Kim S, Estensen RD, Wiedmann TS, Sekar P, Buncher CR, Khoury JC, Garbow JR, You M, Tichelaar JW (2008) Effect of dietary green tea extract and aerosolized difluoromethylornithine during lung tumor progression in A/J strain mice. Carcinogenesis 29(8):1594–1600. doi:10.1093/carcin/bgn129

    Article  PubMed  CAS  Google Scholar 

  25. Fu H, He J, Mei F, Zhang Q, Hara Y, Ryota S, Lubet RA, Chen R, Chen DR, You M (2009) Lung cancer inhibitory effect of epigallocatechin-3-gallate is dependent on its presence in a complex mixture (polyphenon E). Cancer Prev Res (Phila) 2(6):531–537. doi:10.1158/1940-6207.CAPR-08-0185

    Article  CAS  Google Scholar 

  26. Wang Y, Zhang Z, Garbow JR, Rowland DJ, Lubet RA, Sit D, Law F, You M (2009) Chemoprevention of lung squamous cell carcinoma in mice by a mixture of Chinese herbs. Cancer Prev Res (Phila) 2(7):634–640. doi:10.1158/1940-6207.CAPR-09-0052

    Article  Google Scholar 

  27. Wang Y, James M, Wen W, Lu Y, Szabo E, Lubet RA, You M (2010) Chemopreventive effects of pioglitazone on chemically induced lung carcinogenesis in mice. Mol Cancer Ther 9(11):3074–3082. doi:10.1158/1535-7163.MCT-10-0510

    Article  PubMed  CAS  Google Scholar 

  28. Khan N, Afaq F, Kweon MH, Kim K, Mukhtar H (2007) Oral consumption of pomegranate fruit extract inhibits growth and progression of primary lung tumors in mice. Cancer Res 67(7):3475–3482. doi:10.1158/0008-5472.CAN-06-3941

    Article  PubMed  CAS  Google Scholar 

  29. Wang Y, Wen W, Yi Y, Zhang Z, Lubet RA, You M (2009) Preventive effects of bexarotene and budesonide in a genetically engineered mouse model of small cell lung cancer. Cancer Prev Res (Phila) 2(12):1059–1064. doi:10.1158/1940-6207.CAPR-09-0221

    Article  CAS  Google Scholar 

  30. Meuwissen R, Linn SC, Linnoila RI, Zevenhoven J, Mooi WJ, Berns A (2003) Induction of small cell lung cancer by somatic inactivation of both Trp53 and Rb1 in a conditional mouse model. Cancer Cell 4(3):181–189

    Article  PubMed  CAS  Google Scholar 

  31. Lavigueur A, Maltby V, Mock D, Rossant J, Pawson T, Bernstein A (1989) High incidence of lung, bone, and lymphoid tumors in transgenic mice overexpressing mutant alleles of the p53 oncogene. Mol Cell Biol 9(9):3982–3991

    PubMed  CAS  Google Scholar 

  32. Wang Y, Zhang Z, Yao R, Jia D, Wang D, Lubet RA, You M (2006) Prevention of lung cancer progression by bexarotene in mouse models. Oncogene 25(9):1320–1329. doi:10.1038/sj.onc.1209180

    Article  PubMed  CAS  Google Scholar 

  33. Hecht SS (1999) Tobacco smoke carcinogens and lung cancer. J Natl Cancer Inst 91(14):1194–1210

    Article  PubMed  CAS  Google Scholar 

  34. Kassie F, Melkamu T, Endalew A, Upadhyaya P, Luo X, Hecht SS (2010) Inhibition of lung carcinogenesis and critical cancer-related signaling pathways by N-acetyl-S-(N-2-phenethylthiocarbamoyl)-l-cysteine, indole-3-carbinol and myo-inositol, alone and in combination. Carcinogenesis 31(9):1634–1641. doi:10.1093/carcin/bgq139

    Article  PubMed  CAS  Google Scholar 

  35. Zhang Z, Wang Y, Lantry LE, Kastens E, Liu G, Hamilton AD, Sebti SM, Lubet RA, You M (2003) Farnesyltransferase inhibitors are potent lung cancer chemopreventive agents in A/J mice with a dominant-negative p53 and/or heterozygous deletion of Ink4a/Arf. Oncogene 22(40):6257–6265. doi:10.1038/sj.onc.1206630

    Article  PubMed  CAS  Google Scholar 

  36. Wang Y, Zhang Z, Yan Y, Lemon WJ, LaRegina M, Morrison C, Lubet R, You M (2004) A chemically induced model for squamous cell carcinoma of the lung in mice: histopathology and strain susceptibility. Cancer Res 64(5):1647–1654

    Article  PubMed  CAS  Google Scholar 

  37. Rehm S, Lijinsky W, Singh G, Katyal SL (1991) Mouse bronchiolar cell carcinogenesis. Histologic characterization and expression of Clara cell antigen in lesions induced by N-nitrosobis-(2-chloroethyl) ureas. Am J Pathol 139(2):413–422

    PubMed  CAS  Google Scholar 

  38. DuPage M, Dooley AL, Jacks T (2009) Conditional mouse lung cancer models using adenoviral or lentiviral delivery of Cre recombinase. Nat Protoc 4(7):1064–1072. doi:10.1038/nprot.2009.95

    Article  PubMed  CAS  Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Surgery and The Alvin J. Siteman Cancer Center, Washington University School of Medicine, St Louis, MO, USA

    Yian Wang, Michael S. You & Lucina C. Rouggly

  2. Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, WI, USA

    Ming You

Authors
  1. Yian Wang
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  2. Michael S. You
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  3. Lucina C. Rouggly
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  4. Ming You
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Editor information

Editors and Affiliations

  1. The Hormel Institute, Austin, Minnesota, USA

    Ann M. Bode

  2. The Hormel Institute, Austin, Minnesota, USA

    Zigang Dong

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Wang, Y., You, M.S., Rouggly, L.C., You, M. (2014). The Use of Mouse Models for Lung Cancer Chemoprevention Studies. In: Bode, A., Dong, Z. (eds) Cancer Prevention. Methods in Pharmacology and Toxicology. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4614-9227-6_6

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  • DOI: https://doi.org/10.1007/978-1-4614-9227-6_6

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4614-9226-9

  • Online ISBN: 978-1-4614-9227-6

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