Reuben Lotan, Ph.D.
Institutional Affiliation:
Professor
Director of Laboratory Research
Department of Thoracic/Head and Neck Medical Oncology
The University of Texas MD Anderson Cancer Center
http://www.mdanderson.org/departments/thoracic_hnmo/
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Education
Tel Aviv University, M.Sc.
The Weizmann Institute, Rehovoth, Israel, Ph.D.
Postdoctoral Work
The Salk Institute
Research
Characterization of the Lung Tumor Suppressor GPRC5A
Impact
The research provides a new model of lung cancer that is amenable for studies of the mechanisms underlying lung cancer development in order to identify new targets for cancer prevention and therapy as well as new biomarkers for diagnosis and prediction of survival.
Summary of Research
We have discovered a gene, which is now called GPRC5A, which is found primarily in normal lung cells that line the airways and is diminished in lung premalignant and malignant tissues. This suggested that it may function as a tumor suppressor and that its loss is required for human tumors to develop. To examine this hypothesis, we used genetic engineering methods to create a mouse that is missing the mouse homologous gene called Gprc5a. The deficient mice had no apparent problems in development or growth but after 1 year they had began to develop lung tumors of a type called adenocarcinoma. This process was enhanced by exposing the mice to a carcinogen found in tobacco smoke or to an extract of a bacteria that often infects the lungs of humans with a lung disease called chronic obstructive pulmonary disease (COPD). We found that inflammatory cells are infiltrating the lungs of the mutant mice and promote the process of carcinogenesis. These findings suggested that it may be possible to inhibit the process of cancer development by using anti-inflammatory agents. Indeed, we have shown that the agent Budesonide, which is used for treatment of asthma, was able to inhibit lung tumor development in the mice after exposure to a tobacco carcinogen. |
