All PIM kinases are expressed more strongly in aggressive prostate cancer than in benign prostate tissue a study finds
The researchers also observed that the expression of PIM kinases is regulated by ERG oncoproteins. Both findings can be used in the development of new targeted therapies for prostate cancer especially in those patients who have increased expression of these cancer promoting factors.
Prostate cancer is one of the most common cancers in men in Finland. More than 5,000 new diagnoses are made every year, most often based on elevated PSA (prostate-specific antigen) levels. Prostate cancer is treated by surgery or radiation therapy often accompanied by hormonal therapy and possibly cytostatic agents, which are relatively good treatments in most cases. However, some of the cancers will eventually develop into aggressive castration-resistant prostate cancers (CRPC) which no longer respond to hormone deprivation therapy. Thus, new approaches to diagnosing and treating malignant prostate cancers are needed.
The research groups led by Professor Tapio Visakorpi from Tampere University, Docent Päivi Koskinen from the University of Turku and Docent Leena Latonen from the University of Eastern Finland have investigated the interactions of PIM, ERG and MYC proteins in prostate cancer patients.
The overexpression of PIM kinases has previously been shown to increase cell viability, ability, and metastatic growth in prostate cancer. However, comprehensive studies on the expression of PIM kinases during the progression of prostate cancer have not been done before especially at the protein levels.
“We discovered that the expression of all three PIM kinases (PIM1, 2 and 3), and ERG and MYC proteins is often simultaneously enhanced in prostate cancer. PIM kinases are more highly expressed in localised prostate cancer compared to the benign prostate. Furthermore, we discovered that the ERG transcription factor can regulate the expression of all PIM kinases in prostate cancer cells,” explains Doctoral Researcher Sini Eerola from Tampere University.
The results from prostate cancer patient samples indicated that the overexpression of the PIM and ERG proteins was associated with prostate cancer development. Strikingly, the expression of PIM1 and PIM2 proteins was enhanced in castration-resistant prostate cancer which has a poor prognosis.
“According to clinical patient data and our experimental observations, drugs targeting the PIM, ERG and MYC proteins can improve the prospects of patients with increased expression levels of these cancer promoting factors,” Eerola says.
Sini K. Eerola, Annika Kohvakka, Teuvo L. J. Tammela, Päivi J. Koskinen, Leena Latonen, Tapio Visakorpi: Expression and ERG regulation of PIM kinases in prostate cancer. Cancer Medicine, May 2021.
Doctoral student Sini Eerola, sini.eerola [at] tuni.fi