The role of Wilm's tumor gene 1 in lung cancer
Abstracts
Initial Award Abstract |
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Lung cancer is the leading cause of cancer death among both men and women in the US and more than 160,000 lung cancer deaths are expected in 2008. The two main types of lung cancer are small cell lung cancer and non-small cell lung cancer, which comprise 20% and 80% of the lung cancer cases respectively. Lung cancer is a cancer that forms in tissues of the lung, usually in the cells lining air passages. Tobacco exposure and other environmental agents can damage cells in ways that set the cancer process in motion. This damage can be irreversible, leading towards the final development of lung cancer. A specific set of proto-oncogenes can be affected in those cells within the lungs, among Kras is represented. Activation of oncogenic properties of Kras by cell damage can trigger a signaling program that includes a large set of genes. Promotion of this program can be responsible for the final progression of lung cancer.
The aim of this proposal is to study the role of one of these signaling genes, Wt1, in Kras-driven lung cancer. Preliminary results in our lab pointed at Wt1 as a potential regulator of oncogenic Kras effects in lung cancer. We hypothesize that Wt1 may be regulating critical genes that mediate the progression of lung cancers harboring Kras mutations. To address this question, we will focus on several aims. We will first make use of functional in vitro and in vivo experiments using mouse and human lung cancer cell lines with defined Kras mutations to test the implication of Wt1 and signaling components in lung cancer cells. In addition, we will take advantage of mouse genetics to study the role of Wt1 loss in a mouse model of Kras-driven lung tumorigenesis lacking Wt1 expression.
We anticipate that attenuation of Wt1 or related signaling components might have a significant impact on the growth of lung tumors. We plan to transfer the knowledge gained by these experiments to test the importance of Wt1 and other related signaling components in human samples. We expect that some of the genes being part of the presented proposal will have a critical role in human lung cancer patients. Therefore, we hope that the results coming from this study will set the rationale for the development of new therapies that could significantly increase the overall survival of patients with this fatal disease. |
