St. Jude/Mayo Clinic study finds direct link between CBP gene an...( (MEMPHIS TENN.--Feb. 24 2004) Inactiv...)

(MEMPHIS, TENN.--Feb. 24, 2004) Inactivation of the gene CBP in certain immature white blood cells of mice causes lymphoma, a type of cancer also found in humans. The cancer is accompanied by changes in the expression of specific genes associated with development of the disease. These findings, from researchers at St. Jude Children's Research Hospital and the Mayo Clinic, are published in the Feb. 24 issue of Cancer Cell.

The key to the success of this work is the so-called "conditional knockout mouse" developed by the joint St. Jude-Mayo team, according to Paul Brindle, Ph.D., associate member in the St. Jude Department of Biochemistry. In a conditional knockout mouse, a specific gene is rendered inactive in only one type of cell, even though the gene exists in all normal cells of the body.

Brindle is co-author of the Cancer Cell article. The paper's senior author is Jan M. van Deursen, associate professor of Biochemistry and Molecular Biology and associate professor of Pediatrics at Mayo Clinic College of Medicine.

The research suggests that these CPB knockout mice will be a valuable tool in the further study of the role of CBP in the development of lymphomas. In the future, the mouse model might be useful for preclinical testing of novel drugs to treat these cancers.

"One finding that was particularly surprising was the specific effect the loss of CBP had on the mice," Brindle said. "It is commonly believed that CBP is intimately involved in the control of many genes. Yet the absence of CBP appears to promote lymphoma by cooperating with a narrow set of dysregulated genes." Lymphomas are cancers of either B-lymphocytes, which produce antibodies, or T-lymphocytes, a group of cells that either stimulate B cells or orchestrate attacks on cancer cells or invading organisms. In this study, loss of CBP only led to T-cell lymphoma.

Another unexpected finding was the lack of association between the loss of CBP function and a gene called p53
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Contact: Bonnie Cameron
bonnie.cameron@stjude.org
901-495-4815
St. Jude Children's Research Hospital
24-Feb-2004

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