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Defects in critical gene lead to accelerated lung tumor growth

CHAPEL HILL Cancer causing mutations occur in our bodies every day but luckily, we have specific genes that recognize these malignant events and keep cells from growing out of control. Only a few of these genes called tumor suppressors are currently known.

Now scientists at the University of North Carolina at Chapel Hill School of Medicine and Harvard Medical School have added to the list another powerful tumor suppressor, a gene called LKB1. Their research indicates that this gene is mutated in almost a quarter of all human lung cancers. In mice, these mutations result in tumors that are more aggressive and more likely to spread throughout the body.

Defects in this gene appear to result in a much nastier form of lung cancer, a disease that is bad to begin with, said Dr. Norman Sharpless, an assistant professor of medicine and genetics in the UNC School of Medicine, a member of the UNC Lineberger Comprehensive Cancer Center and a senior author of the study. This finding is expected to help doctors better assign a prognosis to their patients, as well as giving them a new target for future therapies, Sharpless said.

The study, published online Aug. 5 in the journal Nature, also presents the first mouse model of the most lethal malignancy in man, a form of lung cancer called squamous cell carcinoma. Lung cancer kills more Americans each year than breast, prostate and colorectal cancers combined. Of the different types of lung cancer, squamous is strongly associated with tobacco use and is the most common worldwide.

Mice genetically engineered to have defects in the LKB1 gene in the lung develop cancer at a much faster rate than those with defects in other tumor suppressors commonly mutated in lung cancer. These mice develop cancers of not just one lung cancer subtype, but exhibit all three forms of non-small cell lung cancer: adenocarcinomas, squamous cell carcinomas and large cell carcinomas. In addition, these cancers
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Contact: L. H. Lang
llang@med.unc.edu
919-843-9687
University of North Carolina School of Medicine
5-Aug-2007


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