Journal of Stem Cell Research & Therapy

A new lung cancer mouse model

3^rd International Conference and Exhibition on Cell & Gene Therapy

October 27-29, 2014 Embassy Suites Las Vegas, USA

Yinling Hu, Zouxiang Xiao, Qun Jiang, Jami Willette-Brown, Sichuan Xi, Feng Zhu, Sandra Burkett, Timothy Back, Na-Young Song, Mahesh Datla, Zhonghe Sun, Romina Goldszmid, Fanching Lin, Travis Cohoon, Kristen Pike, Xiaolin Wu, David S Schrump, Kwok-Kin Wong, Howard A Young, Giorgio Trinchieri and Ro

Accepted Abstracts: J Stem Cell Res Ther

Abstract:

Lung cancer is the leading cause of cancer mortality worldwide. Lung squamous cell carcinoma (SCC), a major type of human lung cancer, has not well been recapitulatedin mice. Here, we report that kinase-dead IKKα knock-in mice develop spontaneous lung SCCs associated with IKKα downregulation and marked pulmonary inflammation. In an epigenetic manner, IKKα reduction upregulated the expression of p63, Trim29, and keratin 5 (K5), which serve as diagnostic markers for human lung SCCs. IKKαlowK5+p63hi cell expansion and SCC formation were accompanied by inflammation-associated deregulation of oncogenes, tumor suppressors, and stem cell regulators. Reintroducing transgenic K5.IKKα, depleting macrophages, and reconstituting irradiated mutant animals with WT bone marrow (BM) prevented SCC development, suggesting that BMderived IKKα-mutant macrophages promote the transition of IKKαlowK5+p63hi cells to tumor cells. This mouse model resembles human lung SCCs, sheds light on the mechanisms underlying lung malignancy development, and identifies targets for therapy of lung SCCs.

Biography :

Yinling Hu did her undergraduate degree in Chinese Academy of Medical Science and received PhD from University of Melbourne at Australia. She was a Postdoctoral fellow in Michael Karins laboratory, University of California at San Diego from 1996 to 2001. She began to establish her laboratory as an Assistant Professor at Science Park Research Division, M.D. Anderson Cancer Center in November 2001 and came to NCI-Frederick as a Principal Investigator in September 2008..