Mouse models of lung cancer : understanding the molecular and cellular basis of lung tumorigenesis

Lung cancer is the leading cause of cancer deaths worldwide. Patients are typically diagnosed with advanced disease and have a high fatality:case ratio. Despite its prevalence, the identity of the cell of origin, precursor lesions and stages of disease progression have not been well characterized for most types of lung cancer. Furthermore, there are no effective screening methods for lung cancer and standard chemotherapeutics are ineffective in treating advanced lung cancer. The work presented here describes the development and characterization of a murine lung cancer model that uses conditional expression of oncogenic K-ras to drive tumorigenesis. The conditional allele is controlled by the Cre-loxP system. Using adenovirus to deliver Cre recombinase to the lungs we have controlled the timing and multiplicity of tumor initiation. We used this model to investigate several aspects of tumor biology. Timecourse experiments revealed the histologic stages of lung tumor progression, advancing from atypical adenomatous hyperplasia to adenoma to adenocarcinoma. Studies of early lesions provided insights into the ras effector pathways required for tumor initiation, implicating the JNK and p38 pathways in this process. In addition, our studies regarding the cell of origin of lung tumors led to the identification of a novel cell type in the adult lung that resembles an embryonic lung precursor cell.

Department dc:contributor.department

Massachusetts Institute of Technology. Dept. of Biology.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2003

Author dc:creator

• Jackson, Erica L. (Erica Lynn), 1973-

Advisor dc:contributor.advisor

• Tyler Jacks.

• Biology.

Statement dc:rights

• M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/29992

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/29992