Expression and ERG regulation of PIM kinases in prostate cancer

Sini K Eerola, Annika Kohvakka, Teuvo L J Tammela, Päivi J. Koskinen, Leena Latonen, Tapio Visakorpi

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Abstract

The three oncogenic PIM family kinases have been implicated in the development of prostate cancer (PCa). The aim of this study was to examine the mRNA and protein expression levels of PIM1, PIM2, and PIM3 in PCa and their associations with the MYC and ERG oncogenes. We utilized prostate tissue specimens of normal, benign prostatic hyperplasia (BPH), prostatic intraepithelial neoplasia (PIN), untreated PCa, and castration-resistant prostate cancer (CRPC) for immunohistochemical (IHC) analysis. In addition, we analyzed data from publicly available mRNA expression and chromatin immunoprecipitation sequencing (ChIP-Seq) datasets. Our data demonstrated that PIM expression levels are significantly elevated in PCa compared to benign samples. Strikingly, the expression of both PIM1 and PIM2 was further increased in CRPC compared to PCa. We also demonstrated a significant association between upregulated PIM family members and both the ERG and MYC oncoproteins. Interestingly, ERG directly binds to the regulatory regions of all PIM genes and upregulates their expression. Furthermore, ERG suppression with siRNA reduced the expression of PIM in PCa cells. These results provide evidence for cooperation of PIM and the MYC and ERG oncoproteins in PCa development and progression and may help to stratify suitable patients for PIM-targeted therapies.

Original languageEnglish
JournalCancer Medicine
Volume10
Issue number10
DOIs
Publication statusPublished - 2021
Publication typeA1 Journal article-refereed

Keywords

  • castration-resistant prostate cancer
  • ERG
  • MYC
  • PIM kinase
  • prostate cancer

Publication forum classification

  • Publication forum level 1

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