Role of the Cdc25A phosphatase in human breast cancer

M. Giulia Cangi, Barry Cukor, Peggy Soung, Sabina Signoretti, Gilberto Moreira, Moksha Ranashinge, Blake Cady, Michele Pagano, Massimo Loda

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)753-761
Number of pages9
JournalJournal of Clinical Investigation
Volume106
Issue number6
Publication statusPublished - Sep 2000

ASJC Scopus subject areas

  • Medicine(all)

Fingerprint Dive into the research topics of 'Role of the Cdc25A phosphatase in human breast cancer'. Together they form a unique fingerprint.

Cite this