Abstract

BackgroundPRL-3 is a phosphatase implicated in oncogenesis in multiple cancers. In some cancers, notably carcinomas, PRL-3 is also associated with inferior prognosis and increased metastatic potential. In this study we investigated the expression of PRL-3 mRNA in fresh-frozen samples from patients undergoing radical prostatectomy because of prostate cancer (PC) and the biological function of PRL-3 in prostate cancer cells.MethodsSamples from 41 radical prostatectomy specimens (168 samples in total) divided into low (Gleason score ≤ 6), intermediate (Gleason score = 7) and high (Gleason score ≥ 8) risk were analyzed with gene expression profiling and compared to normal prostate tissue. PRL-3 was identified as a gene with differential expression between healthy and cancerous tissue in these analyses. We used the prostate cancer cell lines PC3 and DU145 and a small molecular inhibitor of PRL-3 to investigate whether PRL-3 had a functional role in cancer. Relative ATP-measurement and thymidine incorporation were used to assess the effect of PRL-3 on growth of the cancer cells. We performed an in vitro scratch assay to investigate the involvement of PRL-3 in migration. Immunohistochemistry was used to identify PRL-3 protein in prostate cancer primary tumor and corresponding lymph node metastases.ResultsCompared to normal prostate tissue, the prostate cancer tissue expressed a significantly higher level of PRL-3. We found PRL-3 to be present in both PC3 and DU145, and that inhibition of PRL-3 led to growth arrest and apoptosis in these two cell lines. Inhibition of PRL-3 led to reduced migration of the PC3 cells. Immunohistochemistry showed PRL-3 expression in both primary tumor and corresponding lymph node metastases.ConclusionsPRL-3 mRNA was expressed to a greater extent in prostate cancer tissue compared to normal prostate tissue. PRL-3 protein was expressed in both prostate cancer primary tumor and corresponding lymph node metastases. The results from our in vitro assays suggest that PRL-3 promotes growth and migration in prostate cancer. In conclusion, these results imply that PRL-3 has a role in the pathogenesis of prostate cancer.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-016-0830-z) contains supplementary material, which is available to authorized users.

Highlights

  • phosphatase of regenerating liver 3 (PRL-3) is a phosphatase implicated in oncogenesis in multiple cancers

  • We studied whether Phosphatase of regenerating liver (PRL)-3 mRNA and protein were present in freshfrozen prostate samples from patients operated with radical prostatectomy, and whether it had an effect on proliferation and migration in prostate cancer cell lines

  • The results showed that PRL-3 was expressed at detectable mRNA-levels in both of the prostate cancer cell lines PC3 and DU145 (Fig. 2a)

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Summary

Introduction

Notably carcinomas, PRL-3 is associated with inferior prognosis and increased metastatic potential. The morbidity and mortality of cancer is closely related to the spread of metastases. In this process, the tumor cells go through several cellular transformations to be able to colonize distant sites. A key feature of the transformation is the ability to migrate. This ability is acquired as the cell undergoes an epithelial-mesenchymal transition (EMT), which is essential for metastatic dissemination. The process of metastasis is not fully understood, and the definitive role of PRL-3 remains obscure

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