PP1 catalytic isoforms are differentially expressed and regulated in human prostate cancer

Abstract

The Ser/Thr-protein phosphatase PP1 (PP1) is a positive regulator of the androgen receptor (AR), which suggests major roles for PP1 in prostate carcinogenesis. However, studies dedicated to the characterization of PP1 in PCa are currently scarce. Here we analyzed the expression and localization of the PP1 catalytic (PP1c) isoforms in formalin-fixed, paraffin-embedded prostate tissue samples, as well as in PCa cell lines. We also analyzed well-characterized PCa cohorts to determine their transcript levels, identify genetic alterations, and assess promoter methylation of PP1c-coding genes. We found that PP-1A was upregulated and relocalized towards the nucleus in PCa and that PPP1CA was frequently amplified in PCa, particularly in advanced stages. PP-1B was downregulated in PCa but upregulated in a subset of tumors with AR amplification. PP-1G transcript levels were found to be associated with Gleason score. PP1c-coding genes were rarely mutated in PCa and were not prone to regulation by promoter methylation. Protein phosphorylation, on the other hand, might be an important regulatory mechanism of PP1c isoforms' activity. Altogether, our results suggest differential expression, localization, and regulation of PP1c isoforms in PCa and support the need for investigating isoform-specific roles in prostate carcinogenesis in future studies.