Protein linked with lung cancer development

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Published on 21 October 2009, 10:46

Categories: Proteins Lung Cancer NF-kappaB Cancer Biology P53 Tumors Lungs Lung adenocarcinoma

Protein linked with lung cancer development

A protein that normally helps defend cells from infection, known as NF-kappaB, can play a critical role in the development of lung cancer, according to MIT cancer biologists. The MIT team found that a particular pair of genetic circumstances is required to activate NF-kappaB in mouse lung tumors: expression of the cancer gene ras, and loss of the tumor suppressor gene p53. They also showed that inhibition of NF-kappaB in mice with that genetic profile can slow tumor growth.

The findings suggest that NF-kappaB could be a promising target for new drugs against lung cancer, which kills more than one million people each year. Any potential treatments targeting NF-kappaB could be useful in the 15 percent of human lung cancer patients who have the specific genetic mutations required to activate NF-kappaB.

The researchers found that when they inhibited NF-kappaB in mice with lung tumors expressing this genetic profile, tumor growth slowed dramatically. During the three-week period following NF-kappaB inhibition, tumors in treated mice grew, on average, half as much as tumors in untreated mice. In some treated mice, tumors shrank.

The researchers could use their mouse model of lung cancer to look for compounds that could selectively and powerfully inhibit NF-kappaB.

Left: Tumors are visible in the lungs of a mouse in which the NF-kappaB protein is not inhibited. Right: In the lungs of a mouse in which NF-kappaB is inhibited, tumor growth is significantly slowed. Images were taken at the Koch Institute Microscopy and Imaging Core Facility.
Photo - Images: Etienne Meylan, courtesy Nature

Paper: "Requirement for NF-kB signaling in a mouse model of lung adenocarcinoma," Etienne Meylan, Tyler Jacks et al. Nature, Oct. 22, 2009.

Contact: Jen Hirsch, MIT News Office, jfhirsch@mit.edu, 617-253-1682

Source: Massachusetts Institute of Technology

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