Role of the Cdc25A phosphatase in human breast cancer.

TitleRole of the Cdc25A phosphatase in human breast cancer.
Publication TypeJournal Article
Year of Publication2000
AuthorsCangi MG, Cukor B, Soung P, Signoretti S, Moreira G, Ranashinge M, Cady B, Pagano M, Loda M
JournalJ Clin Invest
Date Published2000 Sep
KeywordsBreast Neoplasms, CDC2-CDC28 Kinases, cdc25 Phosphatases, Cyclin-Dependent Kinase 2, Cyclin-Dependent Kinases, Databases, Factual, Enzyme Activation, Female, Gene Expression Regulation, Neoplastic, Histocytochemistry, Humans, Immunoblotting, In Situ Hybridization, Oligonucleotides, Antisense, Phosphorylation, Precipitin Tests, Protein-Serine-Threonine Kinases, Retrospective Studies, Reverse Transcriptase Polymerase Chain Reaction, RNA, Messenger, S Phase, Survival Rate, Time Factors, Transfection, Tumor Cells, Cultured

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.

Alternate JournalJ Clin Invest
PubMed ID10995786
PubMed Central IDPMC381390
Grant ListP30 CA016087 / CA / NCI NIH HHS / United States
R01 GM057587 / GM / NIGMS NIH HHS / United States
R01CA81755 / CA / NCI NIH HHS / United States
P30CA16087 / CA / NCI NIH HHS / United States
R01GM57587 / GM / NIGMS NIH HHS / United States
R01 CA076584 / CA / NCI NIH HHS / United States
Related Faculty: 
Massimo Loda, M.D.

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