Variable Vulnerability to Oncogene

April 15, 2011 | Leigh MacMillan

Mutations that activate the Kras oncogene are common in many epithelial tumors, including cancers of the pancreas, colon and lung, but Kras mutations are rare in cancers of the oral cavity and stomach. Why some tissues are vulnerable to Kras mutations, and some are not, is unclear.

To explore the susceptibility of different epithelial tissues to Kras mutations, Anna Means, Ph.D., and colleagues introduced one of the most common Kras mutations broadly in adult epithelial tissues of the mouse. They report in the journal PLoS ONE that the Kras mutation caused neoplastic changes in some, but not all, tissues. They observed hyperplasias, metaplasias and adenomas in the oral cavity, stomach, colon, and lungs; there were no changes in the small intestines. Metaplasias with characteristics of early stage pancreatic cancer also developed in the pancreas, supporting the hypothesis that pancreatic ducts can give rise to cancer.

The mouse model will be useful for probing the environmental factors and tissue-intrinsic mechanisms that make some tissues more vulnerable than others to Kras activation.

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