Expression and ERG regulation of PIM kinases in prostate cancer

Autor: Leena Latonen, Teuvo L.J. Tammela, Päivi J. Koskinen, Tapio Visakorpi, Annika Kohvakka, Sini K. Eerola
Přispěvatelé: Tampere University, BioMediTech, Department of Surgery, Clinical Medicine, Department of Clinical Chemistry, TAYS Cancer Centre
Jazyk: angličtina
Rok vydání: 2021
Předmět:
0301 basic medicine
castration‐resistant prostate cancer
Male
Cancer Research
Prostatic Hyperplasia
PIM1
MYC
Biology
urologic and male genital diseases
03 medical and health sciences
Prostate cancer
0302 clinical medicine
Proto-Oncogene Proteins c-pim-1
Transcriptional Regulator ERG
Prostate
hemic and lymphatic diseases
medicine
Humans
Radiology
Nuclear Medicine and imaging
RNA
Messenger
RNA
Small Interfering
RC254-282
Original Research
Cancer Biology
Aged
Kinase
PIM kinases
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Prostatic Neoplasms
Hyperplasia
Middle Aged
medicine.disease
prostate cancer
3126 Surgery
anesthesiology
intensive care
radiology
Up-Regulation
Gene Expression Regulation
Neoplastic
030104 developmental biology
medicine.anatomical_structure
Oncology
Regulatory sequence
030220 oncology & carcinogenesis
ERG
Cancer research
Immunohistochemistry
3111 Biomedicine
Erg
Zdroj: Cancer Medicine
Cancer Medicine, Vol 10, Iss 10, Pp 3427-3436 (2021)
Popis: 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.
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 all PIM family genes.
Databáze: OpenAIRE
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