Display options
Cite
Wang Y, Xu Z, Mao JH, et al. Analysis of lung tumor initiation and progression in transgenic mice for Cre-inducible overexpression of Cul4A gene. Thorac Cancer. 2015;6(4):480-7doi: 10.1111/1759-7714.12257.
Wang, Y., Xu, Z., Mao, J. H., Hung, M. S., Hsieh, D., Au, A., Jablons, D. M., & You, L. (2015). Analysis of lung tumor initiation and progression in transgenic mice for Cre-inducible overexpression of Cul4A gene. Thoracic cancer, 6(4), 480-7. https://doi.org/10.1111/1759-7714.12257
Wang, Yang, et al. "Analysis of lung tumor initiation and progression in transgenic mice for Cre-inducible overexpression of Cul4A gene." Thoracic cancer vol. 6,4 (2015): 480-7. doi: https://doi.org/10.1111/1759-7714.12257
Wang Y, Xu Z, Mao JH, Hung MS, Hsieh D, Au A, Jablons DM, You L. Analysis of lung tumor initiation and progression in transgenic mice for Cre-inducible overexpression of Cul4A gene. Thorac Cancer. 2015 Jul;6(4):480-7. doi: 10.1111/1759-7714.12257. Epub 2015 Jun 08. PMID: 26273405; PMCID: PMC4511328.
Copy Download .nbib Format: NLM
Share it on

Thorac Cancer. 2015 Jul;6(4):480-7. doi: 10.1111/1759-7714.12257. Epub 2015 Jun 08.

Analysis of lung tumor initiation and progression in transgenic mice for Cre-inducible overexpression of Cul4A gene.

Thoracic cancer

Yang Wang, Zhidong Xu, Jian-Hua Mao, Ming-Szu Hung, David Hsieh, Alfred Au, David M Jablons, Liang You

Affiliations

  1. Department of Thoracic Surgery, Beijing Chao-Yang Hospital, Capital Medical University Beijing, China.
  2. Thoracic Oncology Laboratory, Department of Surgery, Comprehensive Cancer Center, University of California San Francisco, USA.
  3. Life Sciences Division, Lawrence Berkeley National Laboratory, University of California Berkeley, USA.
  4. Division of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital Chiayi, Taiwan.
  5. Division of diagnostic pathology, Comprehensive Cancer Center, University of California San Francisco, USA.

PMID: 26273405 PMCID: PMC4511328 DOI: 10.1111/1759-7714.12257

Abstract

BACKGROUND: Lung cancer is the leading cause of morbidity and death worldwide. Although the available lung cancer animal models have been informative and further propel our understanding of human lung cancer, they still do not fully recapitulate the complexities of human lung cancer. The pathogenesis of lung cancer remains highly elusive because of its aggressive biologic nature and considerable heterogeneity, compared to other cancers. The association of Cul4A amplification with aggressive tumor growth and poor prognosis has been suggested. Our previous study suggested that Cul4A is oncogenic in vitro, but its oncogenic role in vivo has not been studied.

METHODS: Viral delivery approaches have been used extensively to model cancer in mouse models. In our experiments, we used Cre-recombinase induced overexpression of the Cul4A gene in transgenic mice to study the role of Cul4A on lung tumor initiation and progression and have developed a new model of lung tumor development in mice harboring a conditionally expressed allele of Cul4A.

RESULTS: Here we show that the use of a recombinant adenovirus expressing Cre-recombinase ("AdenoCre") to induce Cul4A overexpression in the lungs of mice allows controls of the timing and multiplicity of tumor initiation. Following our mouse models, we are able to study the potential role of Cul4A in the development and progression in pulmonary adenocarcinoma as well.

CONCLUSION: Our findings indicate that Cul4A is oncogenic in vivo, and this mouse model is a tool in understanding the mechanisms of Cul4A in human cancers and for testing experimental therapies targeting Cul4A.

Keywords: AdenoCre; Cre; Cul4A; lung cancer; mouse models

References

  1. Genes Dev. 2001 Dec 15;15(24):3243-8 - PubMed
  2. Genesis. 2000 Nov-Dec;28(3-4):147-55 - PubMed
  3. J Thorac Oncol. 2010 Apr;5(4):466-71 - PubMed
  4. J Cell Mol Med. 2011 Feb;15(2):350-8 - PubMed
  5. Cell. 2005 Jun 17;121(6):823-35 - PubMed
  6. Nature. 2006 Oct 5;443(7111):590-3 - PubMed
  7. Nature. 2001 Apr 26;410(6832):1111-6 - PubMed
  8. Nat Cell Biol. 2006 Nov;8(11):1277-83 - PubMed
  9. Proc Natl Acad Sci U S A. 2014 Apr 1;111(13):4952-7 - PubMed
  10. J Clin Pathol. 2001 Apr;54(4):257-71 - PubMed
  11. Oncogene. 1999 Sep 20;18(38):5318-24 - PubMed
  12. Genesis. 2011 Mar;49(3):134-41 - PubMed
  13. Genes Dev. 2005 Mar 15;19(6):643-64 - PubMed
  14. Proc Natl Acad Sci U S A. 2014 Jan 7;111(1):255-60 - PubMed
  15. J Thorac Oncol. 2011 Feb;6(2):244-85 - PubMed
  16. Nat Protoc. 2009;4(7):1064-72 - PubMed
  17. Cell Stem Cell. 2009 Jun 5;4(6):525-34 - PubMed

Publication Types

Grant support