Abstract
Purpose
The protein tyrosine phosphatase PRL-3 plays an important role in cancer cell migration, invasion and metastasis. In breast cancer, PRL-3 is overexpressed in 70–75% of tumors and even more frequently in lymph node metastases. Moreover, PRL-3 overexpression in breast cancer is associated with an adverse disease outcome. Aim of this study was to determine the role of PRL-3 in breast cancer cell proliferation, migration and invasion in vitro.
Methods
PRL-3 mRNA expression was evaluated in 6 breast cancer cell lines by quantitative real-time PCR. To investigate the effect of PRL-3 expression in breast cancer cells in vitro we both up- and downregulated PRL-3 expression in breast cancer cells and performed in vitro wound repair cell motility assays and invasion assays. The influence of PRL-3 knockdown in MCF-7 cells on the expression of several gene products involved in cell invasion and cytoskeletal function was evaluated with real-time PCR.
Results
PRL-3 mRNA expression was demonstrated in all breast cancer cell lines evaluated. Knockdown of PRL-3 in MCF-7 cells resulted in decreased proliferation, wound healing and invasion. PRL-3 knockdown in MCF-7 cells resulted in a significant reduction of heparanase, MMP-9, actin gamma-2 and Myosin 9 expression, and significant elevation of E-cadherin.
Conclusions
We conclude that PRL-3 is an important regulatory factor for breast cancer cell proliferation and invasion. Loss of PRL-3 function induces an antimetastatic gene expression profile in breast cancer cells. Due to its role in tumor growth and metastasis, PRL-3 emerges as a new therapeutic target in breast cancer therapy.
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Acknowledgements
We thank Birgit Pers for excellent technical assistance. This work was supported by the fund “Innovative Medical Research” of the University of Muenster Medical School (WÜ 110527).
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IR: manuscript writing, data interpretation, project development and design; MG: data interpretation, project development and design, supervision, manuscript editing; MS: data collection and interpretation, supervision, manuscript editing; NS: data collection and interpretation; LK: supervision and manuscript editing; PW: project development and design; supervision; manuscript editing.
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This work was supported by the fund “Innovative Medical Research” of the University of Muenster Medical School (WÜ 110527).
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For this type of study (in vitro study on established cell lines) formal consent is not required. This article does not contain any studies with animals or patient samples.
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Radke, I., Götte, M., Smollich, M. et al. Expression of PRL-3 regulates proliferation and invasion of breast cancer cells in vitro. Arch Gynecol Obstet 296, 1153–1160 (2017). https://doi.org/10.1007/s00404-017-4542-2
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DOI: https://doi.org/10.1007/s00404-017-4542-2