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.
| Original language | English |
|---|---|
| Journal | Archives of Gynecology and Obstetrics |
| Volume | 296 |
| Issue number | 6 |
| Pages (from-to) | 1153-1160 |
| Number of pages | 8 |
| ISSN | 0932-0067 |
| DOIs | |
| Publication status | Published - 01.12.2017 |
Funding
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). Funding This work was supported by the fund “Innovative Medical Research” of the University of Muenster Medical School (WÜ 110527).
Research Areas and Centers
- Academic Focus: Center for Brain, Behavior and Metabolism (CBBM)
