Role of the Cdc25A phosphatase in human breast cancer. Academic Article uri icon

Overview

abstract

  • The phosphatase Cdc25A plays an important role in cell cycle regulation by removing inhibitory phosphates from tyrosine and threonine residues of cyclin-dependent kinases, and it has been shown to transform diploid murine fibroblasts in cooperation with activated Ras. Here we show that Cdc25A is overexpressed in primary breast tumors and that such overexpression is correlated with higher levels of cyclin-dependent kinase 2 (Cdk2) enzymatic activity in vivo. Furthermore, in the breast cancer cell line MCF-7, Cdc25A activity is necessary for both the activation of Cdk2 and the subsequent induction of S-phase entry. Finally, in a series of small (< 1 cm) breast carcinomas, overexpression of Cdc25A was found in 47% of patients and was associated with poor survival. 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.

publication date

  • September 1, 2000

Research

keywords

  • Breast Neoplasms
  • CDC2-CDC28 Kinases
  • cdc25 Phosphatases

Identity

PubMed Central ID

  • PMC381390

Scopus Document Identifier

  • 0033796031

Digital Object Identifier (DOI)

  • 10.1172/JCI9174

PubMed ID

  • 10995786

Additional Document Info

volume

  • 106

issue

  • 6