Protein is linked to lung cancer development

October 22, 2009 by Anne Trafton
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. Images: Etienne Meylan, courtesy Nature

( -- A protein that normally helps defend cells from infection can play a critical role in the development of lung cancer, according to MIT cancer biologists.

Their findings suggest that the protein, NF-kappaB, could be a promising target for new drugs against lung cancer, which kills more than one million people each year.

NF-kappaB is a transcription factor protein that is normally activated when a cell is under attack from a virus or bacterium. Previous studies have suggested that constant activation of NF-kappaB enhances survival of cells.

In the new study, reported in the Oct. 22 issue of Nature, 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 . They also showed that inhibition of NF-kappaB in mice with that genetic profile can slow .

In human patients, the ras gene is active in 30 percent of patients, and p53 is lost in about 50 percent of tumors, meaning that about 15 percent overall have this combination. Drugs that inhibit NF-kappaB could potentially help treat such tumors, says Etienne Meylan, lead author of the paper and a postdoctoral associate in the laboratory of Tyler Jacks, director of the David H. Koch Institute for Integrative Cancer Research at MIT.

The researchers found that when they inhibited NF-kappaB in lung tumors of mice with 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.

Cancer biologists have been pursuing possible treatments based on NF-kappaB inhibition over the past decade or so, but during the past few years, a handful of studies have shown that inhibiting NF-kappaB can have adverse side effects. Because of that, "some people began to re-evaluate the potential of NF-kappaB as a target," says cancer researcher Sankar Ghosh of Columbia University Medical Center, who was not involved in the research. However, he says the new findings should jump start new efforts to target NF-kappaB in tumors with this specific genetic profile. "This paper shows the effects in such a dramatic and striking way, I think it will re-energize people who are interested in NF-kappaB as a potential target," says Ghosh.

The mouse model used in this study could be useful in those efforts, says Meylan. Additionally, "we could use this model to find better compounds — those that are more selective or more powerful," he says.

Provided by Massachusetts Institute of Technology (news : web)

Related Stories

Recommended for you

Researchers identify gene variants linked to a high-risk children's cancer

September 25, 2017
Pediatric researchers investigating the childhood cancer neuroblastoma have identified common gene variants that raise the risk of an aggressive form of that disease. The discovery may assist doctors in better diagnosing ...

Prostaglandin E1 inhibits leukemia stem cells

September 25, 2017
Two drugs, already approved for safe use in people, may be able to improve therapy for chronic myeloid leukemia (CML), a blood cancer that affects myeloid cells, according to results from a University of Iowa study in mice.

MRI contrast agent locates and distinguishes aggressive from slow-growing breast cancer

September 25, 2017
A new magnetic resonance imaging (MRI) contrast agent being tested by researchers at Case Western Reserve University not only pinpoints breast cancers at early stages but differentiates between aggressive and slow-growing ...

Cancer vaccines need to target T cells that can persist in the long fight against cancer

September 25, 2017
Cancer vaccines may need to better target T cells that can hold up to the long fight against cancer, scientists report.

Lung cancer treatment could be having negative health effect on hearts

September 25, 2017
Radiotherapy treatment for lung cancer could have a negative effect on the health of your heart new research has found.

Alternative splicing, an important mechanism for cancer

September 22, 2017
Cancer, which is one of the leading causes of death worldwide, arises from the disruption of essential mechanisms of the normal cell life cycle, such as replication control, DNA repair and cell death. Thanks to the advances ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.