Expression and ERG regulation of PIM kinases in prostate cancer

Our data demonstrate for the first time that expression levels of all three PIM family kinases can be upregulated during prostate cancer progression and can thereby significantly contribute to this process, especially in cooperation with other co ‐overexpressed oncoproteins, such as MYC and ERG, as shown here. The increased PIM expression levels may in turn be explained by our novel observation that ERG can induce transcription of allPIM family genes. AbstractThe 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 theMYC andERG 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 com pared 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 re gions of ...
Source: Cancer Medicine - Category: Cancer & Oncology Authors: Tags: ORIGINAL RESEARCH Source Type: research