Regulation of prostate stromal fibroblasts by the PIM1 protein kinase

Marina Y. Zemskova, Jin H. Song, Bo Cen, Javier Cerda-Infante, Viviana P. Montecinos, Andrew Kraft

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

The PIM1 oncogene is over-expressed in human prostate cancer epithelial cells. Importantly, we observe that in human hyperplastic and cancerous prostate glands PIM1 is also markedly elevated in prostate fibroblasts, suggesting an important role for this kinase in epithelial/stromal crosstalk. The ability of PIM1 to regulate the biologic activity of stromal cells is demonstrated by the observation that expression of PIM1 kinase in human prostate fibroblasts increases the level and secretion of the extracellular matrix molecule, collagen 1A1 (COL1A1), the pro-inflammatory chemokine CCL5, and the platelet-derived growth factor receptors (PDGFR). PIM1 is found to regulate the transcription of CCL5. In co-cultivation assays where PIM1 over-expressing fibroblasts are grown with BPH1 prostate epithelial cells, PIM1 activity markedly enhances the ability of these fibroblasts to differentiate into myofibroblasts and express known markers of cancer-associated fibroblasts (CAFs). This differentiation can be reversed by the addition of small molecule PIM kinase inhibitors. Western blots demonstrate that PIM1 expression in prostate fibroblasts stimulates the phosphorylation of molecules that regulate 5'Cap driven protein translation, including 4EBP1 and eIF4B. Consistent with the hypothesis that the kinase controls translation of specific mRNAs in prostate fibroblasts, we demonstrate that PIM1 expression markedly increases the level of COL1A1 and PDGFRβ mRNA bound to polysomes. Together these results point on PIM1 as a novel factor in regulation of the phenotype and differentiation of fibroblasts in prostate cancer by controlling both the transcription and translation of specific mRNAs.

Original languageEnglish (US)
Pages (from-to)135-146
Number of pages12
JournalCellular Signalling
Volume27
Issue number1
DOIs
StatePublished - Jan 1 2015
Externally publishedYes

Fingerprint

Protein Kinases
Prostate
Fibroblasts
Protein Biosynthesis
Phosphotransferases
Platelet-Derived Growth Factor Receptors
Prostatic Neoplasms
Collagen
Epithelial Cells
Chemokine CCL5
Polyribosomes
Myofibroblasts
Stromal Cells
Oncogenes
Extracellular Matrix
Western Blotting
Phosphorylation
Phenotype
Messenger RNA

Keywords

  • CCL5
  • COL1A1
  • Myofibroblasts
  • PDGDRβ
  • PIM1 kinase
  • Prostate cancer

ASJC Scopus subject areas

  • Cell Biology

Cite this

Zemskova, M. Y., Song, J. H., Cen, B., Cerda-Infante, J., Montecinos, V. P., & Kraft, A. (2015). Regulation of prostate stromal fibroblasts by the PIM1 protein kinase. Cellular Signalling, 27(1), 135-146. https://doi.org/10.1016/j.cellsig.2014.10.010

Regulation of prostate stromal fibroblasts by the PIM1 protein kinase. / Zemskova, Marina Y.; Song, Jin H.; Cen, Bo; Cerda-Infante, Javier; Montecinos, Viviana P.; Kraft, Andrew.

In: Cellular Signalling, Vol. 27, No. 1, 01.01.2015, p. 135-146.

Research output: Contribution to journalArticle

Zemskova, MY, Song, JH, Cen, B, Cerda-Infante, J, Montecinos, VP & Kraft, A 2015, 'Regulation of prostate stromal fibroblasts by the PIM1 protein kinase', Cellular Signalling, vol. 27, no. 1, pp. 135-146. https://doi.org/10.1016/j.cellsig.2014.10.010
Zemskova, Marina Y. ; Song, Jin H. ; Cen, Bo ; Cerda-Infante, Javier ; Montecinos, Viviana P. ; Kraft, Andrew. / Regulation of prostate stromal fibroblasts by the PIM1 protein kinase. In: Cellular Signalling. 2015 ; Vol. 27, No. 1. pp. 135-146.
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