Abstract
Tyrosine phosphorylation is controlled by a balance of tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs). Whereas the contribution of PTKs to breast tumorigenesis is the subject of intense scrutiny, the potential role of PTPs is poorly known. RPTPα is implicated in the activation of Src family kinases, and regulation of integrin signaling, cell adhesion, and growth factor responsiveness. To explore its potential contribution to human neoplasia, we surveyed RPTPα protein levels in primary human breast cancer. We found RPTPα levels to vary widely among tumors, with 29% of cases manifesting significant overexpression. High RPTPα protein levels correlated significantly with low tumor grade and positive estrogen receptor status. Expression of RPTPα in breast carcinoma cells led to growth inhibition, associated with increased accumulation in G0 and G1, and delayed tumor growth and metastasis. To our knowledge, this is the first example of a study correlating expression level of a specific bona fide PTP with neoplastic disease status in humans.
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Abbreviations
- PTK:
-
protein tyrosine kinase
- PTP:
-
protein tyrosine phosphatase
- RTK:
-
receptor tyrosine kinase
- SFK:
-
Src family kinase
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Acknowledgements
Supported by NIH (R29 CA68365 to J Sap; NCI core support grant P30CA16087), U.S. Department of Defense (DAMD17-98-1-8136 to J Sap), and Associazione Italiana per la Ricerca sul Cancro (to E Ardini and S Ménard). J Sap is the recipient of an Irma T Hirschl career scientist award. Work was initiated through a pilot project under NIH breast cancer program development grant 5R21 CA66229-04. We appreciated comments on the manuscript by Drs G Inghirami, J Melamed, A Pellicer and F Symmans. We thank Dr P Lollini for N202.1A cells, F Castiglioni for help with figures, and C Ghirelli for technical assistance.
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Ardini, E., Agresti, R., Tagliabue, E. et al. Expression of protein tyrosine phosphatase alpha (RPTPα) in human breast cancer correlates with low tumor grade, and inhibits tumor cell growth in vitro and in vivo. Oncogene 19, 4979–4987 (2000). https://doi.org/10.1038/sj.onc.1203869
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DOI: https://doi.org/10.1038/sj.onc.1203869
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