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Cellular molecule spurs growth of prostate cancer

CHAPEL HILL University of North Carolina at Chapel Hill scientists have identified a molecule that stimulates the aggressive growth of prostate cancer. The molecule, Ack1, a member of the growth-promoting tyrosine kinase gene family, stimulates tumor formation in part by signaling prostate cells to rid themselves of a tumor-suppressor protein. Normally, this suppressor protein would inhibit rapid cell growth by signaling the cell to destroy itself.

A report on the study, which appeared Nov. 15 in the journal Cancer Research, also points to Ack1 as a potential target for developing novel drugs against prostate cancer.

The study's senior author, Dr. Shelton Earp, directs the UNC Lineberger Comprehensive Cancer Center and is Lineberger professor of cancer research and a professor of pharmacology and medicine.

Tests of Ack1 demonstrate a profound effect on tumor growth in experimental systems, Earp said. "It's a remarkable effect. Tumors grew more rapidly and invaded as if they were converted to advanced prostate cancer."

Another major finding of the study involved an experimental drug developed by the National Cancer Institute, called geldanamycin. In laboratory tests, the UNC Lineberger group found Ack1 activity could be inhibited through interference with its molecular interactions, thus offering a target for treatment. First, the group discovered that Ack1 bound to a protein called Hsp90 (heat shock protein 90), which associated with many oncogenic, or cancer-causing, signaling proteins.

"If you add geldanamycin to the prostate cancer cell, the drug knocks Hsp90 off oncogenic signaling molecules. This dramatically decreases Ack1 activity and slows tumor formation," Earp said.

In addition, the team compared Ack1 activation in advanced prostate cancer tissue from patients with that found in benign prostatic hypertrophy, or non-cancerous prostate enlargement. The team showed the levels of the activated Ack1 to be much higher i
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Contact: L. H. Lang
llang@med.unc.edu
919-843-9687
University of North Carolina School of Medicine
29-Nov-2005


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