National Cancer Institute (NCI) investigators have designed a genetically engineered mouse for use in the study of human lung squamous cell carcinoma (SCC).
SCC is a type of non-small cell lung carcinoma, one of the most common types of lung cancer, with a five-year survival rate of about 15 percent. The investigators designed mouse models because they are an essential part of drug development, often the first step after laboratory experiments. The results of this study, headed by Yinling Hu, Ph.D., an investigator in the Laboratory of Experimental Immunology, Center for Cancer Research, NCI, appeared in Cancer Cell, April 15, 2013.
Scientists in this study designed their mouse models to identify molecular targets, such as IKK-alpha (IKK-α), which is a type of enzyme involved in regulating cellular growth, survival and immunity. For more than 10 years, work in Hu’s laboratory has focused on understanding IKK-α’s developmental function in keratinocytes (a type of cell that can give rise to SCC in the skin) by using mice genetically modified by IKK-α deletion, mutation and/or overexpression of IKK-α.
In this study, Hu and colleagues searched for similarities between human and mouse lung SCCs at both the level of the lung SCC cells themselves, as well as the tumor microenvironment in the lungs. As a result, they found that IKK-α reduction elevates levels of cancer-causing proteins, and lowers levels of tumor suppressive proteins in lung SCCs. Further, the mice with the IKK-α reduction exhibited an increase of inflammatory cells in their lungs, which contributed to the initiation and development of lung SCC.
- Zuoxiang 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, Robert H. Wiltrout, Yinling Hu. The Pivotal Role of IKKα in the Development of Spontaneous Lung Squamous Cell Carcinomas. Cancer Cell, 2013; 23 (4): 527 DOI: 10.1016/j.ccr.2013.03.009
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