Androgen-independent human prostate cancer cell lines PC3 and DU145 were transfected with pim-1-targeted or control shRNA, and MTT results revealed that pim-1 knockdown significantly inhibited PC3 and DU145 cell viability in a time-dependent manner (P<0.01).
Based on our data, phosphorylation of PIM1 target sites stimulates NFATC1 activity and enhances its ability to promote prostate cancer cell migration and invasion.
A mouse c-MYC/Pim1-transduced tissue recombination PC model, Myc-CaP allografts, and human PC xenografts were treated with AZD1208 (n = 5-11 per group).
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.
PIM1 kinase is overexpressed in high-grade prostate intraepithelial neoplasia and in prostate cancer compared to normal prostatic tissue and benign prostate hyperplasia.
To explore the role of Pim1 in prostate cancer, we generated conditional Pim1 transgenic mice, expressed Pim1 in prostate epithelium, and analyzed the contribution of PIM1 to neoplastic initiation and progression.
In vitro kinase assays confirmed that PIM1 can phosphorylate AR S213 in a ligand-independent manner and cell type-specific phosphorylation was observed in prostate cancer cell lines.
These results indicate that PIM1 may be necessary to maintain tumorigenicity, and further support efforts aimed at developing PIM1 inhibitors for prostate cancer therapy.
As AR turnover has been previously shown to be critical for cell cycle progression in prostate cancer cells, PIM-1 kinase isoforms may promote prostate cancer cell growth, at least in part, through modulating AR activity via distinct mechanisms.
To identify proliferative signaling pathways that are regulated by PIM kinases we analyzed gene expression differences in DU-145 and PC3 prostate cancer derived cells induced by treatment with the recently developed highly selective PIM kinase inhibitor M-110.
Whereas elevated levels of PIM1 and PIM2 were mostly found in hematologic malignancies and prostate cancer, increased PIM3 expression was observed in different solid tumors.
These findings are important because they provide what we believe to be the first in vivo evidence that treatment of prostate cancer may be possible by targeting PIM-1 using an Ab-based therapy.
Our results support the hypothesis that PIM-1 and hK2 play a significant role in the growth of PCa and the detection of PIM-1 and hK2 mRNA expressions by QRT-PCR provided more reliable and helpful information on diagnosis, treatment, and prognosis of PCa.