Washington (H24N). Too much Cdc25A phosphatase enzyme unleashed in the body can trigger unregulated cell growth that has been linked with increased mortality rates in women with breast cancer, according to a recent study.

The study, which examines the role that Cdc25A plays in breast cancer, is published in the Journal of Clinical Investigation.

Lead investigator M. Guilia Cangi, MD, of the Dana Farber Cancer Institute and colleagues found that Cdc25A strips other phosphates that repress cell growth from various protein residues belonging to enzymes that spark phosphate growth cycles. The most important of these is the cyclin-dependent kinase called E-Cdk2.

"In a series of small breast carcinomas, overexpression of Cdc25A was found in 47 percent of patients and was associated with poor survival," wrote the study's authors. "These data suggest that overexpression of Cdc25A contributes to the biological behavior of primary breast tumors and that both Cdc25A and Cdk2 are suitable therapeutic targets in early-stage breast cancer."

Cangi and colleagues evaluated the expression of Cdc25A in breast tissue taken from 144 patients with early-stage (T1a,b) breast cancer. They found that in a breast cancer cell line that overexpresses Cdc25A, transfection or injection with RNA material such as antisense oligonucleotides, markedly reduced both Cdc25A protein levels and Cdk2 enzymatic activity after a day or two.

In fact, the transfection stopped the breast cancer cells in their tracks before they had advanced in the cell cycle. The researchers think this supports the idea that "Cdc25A-mediated dephosphorylation of Cdk2 is required for cell cycle progression."

Furthermore, about half of the breast tumors evaluated in the study had a high expression of Cdc25A, while little or no Cdc25A expression could be found in normal breast tissue. Patients whose tumors overexpressed Cdc25A had a 24 percent mortality rate, compared with a 5 percent mortality rate in patients with no Cdc25A expression.

"Our study suggests that adjuvant therapy, which benefits patients with advanced breast cancer, may also be appropriate for patients with [early stage] T1a,b disease whose tumors have lost p27 [genes] and overexpress Cdc25A," conclude the researchers. "Specific inhibitors of both Cdc25A and cyclin-dependent kinases such as Cdk2, should they become available, may prove to be particularly useful in this setting."

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