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Cancer drug resistance research leads to possible therapeutic target for Alzheimer's disease

A protein that allows human cancer to resist multiple anticancer drugs also appears to play a key role in Alzheimer's disease, according to research conducted at Fox Chase Cancer Center. The protein, active in brain tissue, could be a target for new drugs to treat patients with Alzheimer's.

The report will appear in advance online publication the of the prestigious Federation of American Societies for Experimental Biology Journal (www.fasebj.org) on May 20, and will appear in the journal's July issue. The research was conducted in the Fox Chase laboratory of Kenneth D. Tew, Ph.D., D.Sc.

Tew's research has largely concentrated on understanding and circumventing mechanisms of cellular resistance to anticancer drugs and understanding cellular pathways that affect drug response and resistance. The new report concerns the human ABCA2 transporter, one of a large family of ATP-binding proteins that transport a variety of molecules across biological membranes.

ATP (adenosine triphosphate) is present in all living cells and serves as a major energy source for cellular reactions. Related transporter proteins with varying functions (there are over 50 coded for by the human genome) are widely expressed in human tissues according to Tew.

"The overexpression of the ABCA2 protein has been implicated in acquired resistance of tumors to the drug estramustine, which is used to treat prostate cancer patients," explained Tew, senior author of the paper. "This transporter is also expressed at high levels in brain tissue and may be linked with the transport of molecules relevant to the etiology of Alzheimer's disease, including those involved in the formation of amyloid plaques. The association of the transporter with Alzheimer's first emerged from a comparative gene expression pattern analysis that we did."

To analyze small changes in gene expression with little material, his laboratory developed Amplified Differential G
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Contact: Karen C. Mallet
k_carter@fccc.edu
215-728-2700
Fox Chase Cancer Center
20-May-2004


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