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M. D. Anderson researchers identify tumor-suppressor gene for lung cancer
Date:11/13/2007

HOUSTON - The GPRC5A gene, which is under-expressed in human lung cancer cells, suppresses lung tumors in mouse models and could provide a key to attacking lung cancer in humans, researchers at The University of Texas M. D. Anderson Cancer Center report in the Nov. 21 edition of The Journal of the National Cancer Institute.

The study found that mice with both of their GPRC5A genes suppressed developed normally until their second year of life, when 76 percent developed precancerous lesions called adenomas in their lungs and another 17 percent developed malignancies called adenocarcinomas. Only 10 percent of mice with both GPRC5A genes intact developed adenomas, and only 11 percent with one working version of the gene. None of the mice in the latter two groups developed lung cancer.

"In humans, lung adenocarcinomas are the most common type of lung cancer and the major cause of death from this disease," says senior author Reuben Lotan, Ph.D., professor in M. D. Anderson's Department of Thoracic/ Head and Neck Medical Oncology. "Further study substantiating the role of the GPRC5A gene in human lung cancer could lead to the development of novel approaches for lung cancer prevention, diagnosis and treatment."

Lung cancer is the leading cause of deaths by cancer, killing 160,000 Americans annually.

Lotan and colleagues earlier had shown that Gprc5a protein is detected in the lungs more than in any other tissue and that it is underexpressed in human non-small cell lung cancer and in head and neck squamous cell carcinoma.

The mouse model experiments were designed to follow-up on these early clues of a tumor-suppressing role for the gene. Loss of a tumor-suppressor gene product such as Gprc5a protein is an important step in cancer development.

The team also found that the tumors generated in the mice without the genes lacked mutations to the K-Ras gene, a common oncogene that fuels cancer growth. "This may be impo
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Contact: Scott Merville
sdmervil@mdanderson.org
713-792-0661
University of Texas M. D. Anderson Cancer Center
Source:Eurekalert

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