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Penn study on silencing of tumor suppressor gene suggests new target for lymphoma
Date:8/9/2011

221.10.254.64

PHILADELPHIA Mariusz A. Wasik, MD, professor of Pathology and Laboratory Medicine, and Qian Zhang, MD, PhD, research assistant professor, both from the Perelman School of Medicine at the University of Pennsylvania, and their colleagues, found that a cancer-causing fusion protein works by silencing the tumor suppressor gene IL-2R common gamma-chain (IL-2Rγ). The results, which appeared in a recent Proceedings of the National Academy of Sciences, suggest news targets for lymphoma and other types of cancer.

Fusion proteins are created by two genes -- originally coding for separate proteins -- joining together. Translation of the fusion gene into an active protein results in a molecule with properties derived from each of the originals. Fusion proteins are relatively commonly found in cancer cells.

The team looked at a fusion protein called NPM-ALK. Anaplastic lymphoma kinase (ALK), which physiologically is expressed only by neurons in fetal life, causes cancer when it is mistakenly expressed in non-neural tissues as a fusion protein with nucleophosphin (NPM) and other partners. NPM-ALK works by silencing the tumor suppressor gene IL-2Rγ. The ALK fusion genes are active in several cancer types including some carcinomas of the lung, thyroid, and kidney.

The protein IL-2Rγ is shared by receptors for several proteins called cytokines that play key roles in the maturation and growth of normal immune cells called CD4+ T cells. The Penn team found that IL-2Rγ expression is inhibited in T-cell lymphoma cells expressing NPM-ALK as a result of epigenetic silencing. The IL-2Rγ gene promoter is silenced by a chemical change to the DNA itself, in this case, the adding of a methyl group to DNA's molecular backbone.

Role of Epigenetic Silencing

Epigenetic gene silencing represents an important mechanism of inhibiting tumor suppressor gene expression in cancer cells.
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Contact: Karen Kreeger
karen.kreeger@uphs.upenn.edu
215-349-5658
University of Pennsylvania School of Medicine
Source:Eurekalert

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