Identification of PRL1 as a novel diagnostic and therapeutic target for castration-resistant prostate cancer by the Escherichia coli ampicillin secretion trap (CAST) method

摘要

Objectives: Although chemotherapy for castration-resistant prostate cancer (CRPC) has been applied clinically in recent years, the effects are not sufficient. It is urgently necessary to develop novel therapeutics for CRPC. We previously generated Escherichia coli ampicillin secretion trap libraries of 2 prostate cancer (PCa) cell lines and normal prostate. By comparing the E. coli ampicillin secretion trap libraries of CRPC cell lines with those of androgen-sensitive PCa cell lines and normal prostate, we focused on the protein-tyrosine-phosphatase of regenerating liver 1 (PRL1) gene and analyzed its expression and biological function. Materials and methods: The expression of PRL1 was examined by quantitative reverse transcription polymerase chain reaction and immunohistochemistry in clinical PCa samples. The effects of PRL1 on PCa cells were evaluated by cell growth, migration, and invasion assays. To investigate the effect of PRL1 on epidermal growth factor receptor (EGFR) signaling, PRL1 knockdown PC3 cells were examined by Western blot and immunohistochemical analyses. Results: Quantitative reverse transcription polymerase chain reaction revealed that PRL1 was expressed much more highly in PCa than in nonneoplastic prostate samples. High expression of PRL1 detected by immunohistochemistry correlated with poor prognosis after prostatectomy and combined androgen blockade therapy. Functional analysis indicated that PRL1 stimulated cell growth, migration, and invasion in PCa cell lines. Expression EGFR and matrix metalloproteinase 9 was reduced by knockdown of PRL1 in the PC3 cell line. Conclusions: PRL1 regulates expression of EGFR and modulates downstream targets. PRL1 has potential as a therapeutic target in PCa including CRPC.