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Phosphatase of regenerating liver-3 (PRL-3) is associated with metastasis and poor prognosis in gastric carcinoma.

ABSTRACT: BACKGROUND: PRL-3 is a member of phosphatases of regenerating liver family, characterized by phosphatase active domain and C-terminal prenylation motif. Overexpression of PRL-3 has been implicated in multiple cancers. Here we examined the clinical significance of PRL-3 in gastric cancer together with its metastatic biological functions utilizing different structural mutants. METHODS: PRL-3 expression was analyzed immunohistochemically in 196 gastric cancer patients and 21 cases of liver metastasis. A series of wild type PRL-3 or its mutant plasmids were expressed in BGC823 cells to investigate the relationship between its catalytic activity, cellular localization and metastatic potential in vitro. RESULTS: Positive staining of PRL-3 was observed in 19.4% (38/196) gastric cancer tissues compared with 76.2% (16/21) in liver metastasis. Statistical analysis revealed that PRL-3 expression correlated with lymph node metastasis and vascular invasion (P<0.05). Patients with high PRL-3 expression showed poorer 5-year overall survival (P=0.011). Wild type PRL-3 expressing cells resulted in enhanced migration and invasion ability, which were greatly crippled in form of PRL-3(C104S) or PRL-3(?CAAX) mutants accompanied with its alteration in subcellular localization. CONCLUSIONS: Metastasis associated protein PRL-3 may serve as a potential prognostic biomarker in human gastric cancer. Both the phosphatase catalytic activity and cellular localization are critical for its function.

SUBMITTER: Xing X

PROVIDER: S-EPMC3878674 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Project description:PRL-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.Samples 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.Compared 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.PRL-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.

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Phosphatase of regenerating liver-3 (PRL-3) is associated with metastasis and poor prognosis in gastric carcinoma.

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