PIAS1 is increased in human prostate cancer and enhances proliferation through inhibition of p21

Julia Hoefer, Georg Schäfer, Helmut Klocker, Holger H H Erb, Ian G Mills, Ludger Hengst, Martin Puhr, Zoran Culig

Research output: Contribution to journalArticlepeer-review

54 Citations (Scopus)


Prostate cancer development and progression are associated with alterations in expression and function of elements of cytokine networks, some of which can activate multiple signaling pathways. Protein inhibitor of activated signal transducers and activators of transcription (PIAS)1, a regulator of cytokine signaling, may be implicated in the modulation of cellular events during carcinogenesis. This study was designed to investigate the functional significance of PIAS1 in models of human prostate cancer. We demonstrate for the first time that PIAS1 protein expression is significantly higher in malignant areas of clinical prostate cancer specimens than in normal tissues, thus suggesting a growth-promoting role for PIAS1. Expression of PIAS1 was observed in the majority of tested prostate cancer cell lines. In addition, we investigated the mechanism by which PIAS1 might promote prostate cancer and found that down-regulation of PIAS1 leads to decreased proliferation and colony formation ability of prostate cancer cell lines. This decrease correlates with cell cycle arrest in the G0/G1 phase, which is mediated by increased expression of p21(CIP1/WAF1). Furthermore, PIAS1 overexpression positively influences cell cycle progression and thereby stimulates proliferation, which can be mechanistically explained by a decrease in the levels of cellular p21. Taken together, our data reveal an important new role for PIAS1 in the regulation of cell proliferation in prostate cancer.

Original languageEnglish
Pages (from-to)2097-107
Number of pages11
JournalThe American journal of pathology
Issue number5
Publication statusPublished - May 2012

Bibliographical note

Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.


  • Apoptosis
  • Cell Cycle Checkpoints
  • Cell Line, Tumor
  • Cell Proliferation
  • Cyclin-Dependent Kinase Inhibitor p21
  • Down-Regulation
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • Humans
  • Male
  • Neoplasm Proteins
  • Neoplastic Stem Cells
  • Prostate
  • Prostatic Neoplasms
  • Protein Inhibitors of Activated STAT
  • RNA, Messenger
  • RNA, Neoplasm
  • RNA, Small Interfering
  • Small Ubiquitin-Related Modifier Proteins

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