Role of the Cdc25A phosphatase in human breast cancer

The phosphatase Cdc25A plays an important role in cell cycle regulation by removing inhibitory phosphates from tyrosine and threonine residues of cycl in-dependent kinases, and it has been shown to transform diploid murine fib roblasts in cooperation with activated Ras. Here we show that Cdc25A is ove rexpressed in primary breast tumors and that such overexpression is correla ted with higher levels of cyclin-dependent kinase 2 (Cdk2) enzymatic activi ty in vivo. Furthermore, in the breast cancer cell line MCF-7, Cdc25A activ ity is necessary for both the activation of Cdk2 and the subsequent inducti on of S-phase entry. Finally, in a series of small (< 1 cm) breast carcinom as, overexpression of Cdc25A was found in 47% of patients and was associate d with poor survival. These data suggest that overexpression of Cdc25A cont ributes to the biological behavior of primary breast tumors and that both C dc25A and Cdk2 are suitable therapeutic targets in early-stage breast cance r.