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Role of the Cdc25A phosphatase in human breast cancer
M. Giulia Cangi, … , Michele Pagano, Massimo Loda
M. Giulia Cangi, … , Michele Pagano, Massimo Loda
Published September 15, 2000
Citation Information: J Clin Invest. 2000;106(6):753-761. https://doi.org/10.1172/JCI9174.
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Role of the Cdc25A phosphatase in human breast cancer

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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.

Authors

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

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Figure 2

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Cdc25A is overexpressed in human breast cancer. (a) Hematoxylin-and-eosi...
Cdc25A is overexpressed in human breast cancer. (a) Hematoxylin-and-eosin stain of invasive ductal carcinoma of the breast (T). Normal ducts are seen in the lower left corner (N). (b) In situ hybridization with digoxigenin-labeled, antisense riboprobe for Cdc25A demonstrates high expression levels of the phosphatase in tumor cells. Scant to no expression is seen in the adjacent normal breast tissue. (c) Representative example of a nonexpresser: no expression of Cdc25A is seen in the infiltrating ductal carcinoma cells. Scattered residual normal ducts (N) show weak expression of the phosphatase. (d) Representative example of a low expresser for Cdc25A: most infiltrating ductal carcinoma cells do not express Cdc25A mRNA. Rare ducts (arrowhead) show weak expression of the phosphatase. (e and f) Representative examples of high expressers for cdc25A: all infiltrating ductal carcinoma cells show strong staining with the antisense riboprobe for Cdc25A (Panels b, c, d, e, and f: alkaline phosphatase: nitro blue tetrazolium cytoplasmic reaction product, section counterstained with methyl green). Sense controls were negative (not shown).

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ISSN: 0021-9738 (print), 1558-8238 (online)

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