Abstract
Protein tyrosine phosphatase γ (PTPγ) is a member of the receptor-like family of tyrosine phosphatases and has been implicated as a tumor suppressor gene in kidney and lung cancers. Based on our previous findings, we hypothesize that PTPγ is a potential estrogen-regulated tumor suppressor gene in human breast cancer. To examine the effects of PTPγ on growth of MCF-7 human breast cancer cells and compare the estrogenic responses of human breast cells with different PTPγ expression levels, we established several stably transfected MCF-7 cell lines expressing different levels of PTPγ, which were confirmed by RT–PCR and immunostaining. In our work, we used the antisense construct to breakdown endogenous PTPγ level in MCF-7 cells. The results from doubling time assay suggested that PTPγ is capable of inhibiting MCF-7 breast cancer cell growth. We further demonstrated that PTPγ is able to inhibit anchorage-independent growth of breast cancer cells in soft agar and reduce the estrogenic responses of MCF-7 cell proliferation to estradiol-17β (E2) and zeranol (Z, a nonsteroidal growth promoter with estrogenic activity). Our data suggest that PTPγ may function as an important modulator in regulating the process of tumorigenesis in human breast.
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Acknowledgements
This study was supported by Department of Defense Breast Cancer Research Program Grants DAMD 8140 and 9341, and NIH Grants CA 94718 and CA 95915. MIUR 60%, Fondazione Cassa di Risparmio di Verona (Bando 2001) and Consorzio per gli Studi Universitari in Verona, Italy. We thank Dr Kay Huebner for the critical reading of this manuscript.
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Liu, S., Sugimoto, Y., Sorio, C. et al. Function analysis of estrogenically regulated protein tyrosine phosphatase γ (PTPγ) in human breast cancer cell line MCF-7. Oncogene 23, 1256–1262 (2004). https://doi.org/10.1038/sj.onc.1207235
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DOI: https://doi.org/10.1038/sj.onc.1207235
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