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Prostasin regulates iNOS and cyclin D1 expression by modulating protease-activated receptor-2 signaling in prostate epithelial cells.
Prostate. 2009 Dec 01; 69(16):1790-801.P

Abstract

BACKGROUND

Prostasin is down-regulated during inflammation and in invasive cancers, and plays a role in regulation of inflammatory gene expression and invasion.

METHODS

We used the human benign prostatic hyperplasia cell line BPH-1 to investigate gene expression changes associated with siRNA-mediated loss of prostasin expression. Quantitative PCR and/or western blotting were used to evaluate the expression changes of iNOS, ICAM-1, cyclin D1, IL-6, and IL-8. Gene expression changes were also evaluated in the presence of a PAR-2 antagonist. The PC-3 human prostate cancer cell line was used for evaluation of gene expression in response to prostasin re-expression.

RESULTS

Prostasin silencing in BPH-1 was associated with up-regulation of iNOS, ICAM-1, IL-6, and IL-8, and down-regulation of cyclin D1; as well as reduced proliferation and invasion. The iNOS up-regulation and cyclin D1 down-regulation associated with prostasin silencing were inhibited by a PAR-2 antagonist. Re-expression of prostasin, a serine active-site mutant, and a GPI-anchor-free mutant, in the PC-3 cells resulted in PAR-2 and cyclin D1 transcription up-regulation. Transcription up-regulation of IL-6 and IL-8 was associated with re-expression of the serine active-site mutant prostasin in the PC-3 cells. Transcription up-regulation of IL-8, but to a lesser extent, was also observed in PC-3 cells expressing the wild-type prostasin. Expression of a serine protease active prostasin, GPI-anchored or anchor-free, prevented the IL-6 induction in response to PAR-2. The GPI-anchor-free prostasin also prevented the IL-8 induction.

CONCLUSIONS

Prostasin plays a negative regulatory role on PAR-2-mediated signaling in prostate epithelial cells.

Authors+Show Affiliations

Department of Molecular Biology and Microbiology, Burnett School of Biomedical Sciences, University of Central Florida College of Medicine, Orlando, Florida, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19670249

Citation

Chen, Li-Mei, et al. "Prostasin Regulates iNOS and Cyclin D1 Expression By Modulating Protease-activated Receptor-2 Signaling in Prostate Epithelial Cells." The Prostate, vol. 69, no. 16, 2009, pp. 1790-801.
Chen LM, Hatfield ML, Fu YY, et al. Prostasin regulates iNOS and cyclin D1 expression by modulating protease-activated receptor-2 signaling in prostate epithelial cells. Prostate. 2009;69(16):1790-801.
Chen, L. M., Hatfield, M. L., Fu, Y. Y., & Chai, K. X. (2009). Prostasin regulates iNOS and cyclin D1 expression by modulating protease-activated receptor-2 signaling in prostate epithelial cells. The Prostate, 69(16), 1790-801. https://doi.org/10.1002/pros.21030
Chen LM, et al. Prostasin Regulates iNOS and Cyclin D1 Expression By Modulating Protease-activated Receptor-2 Signaling in Prostate Epithelial Cells. Prostate. 2009 Dec 1;69(16):1790-801. PubMed PMID: 19670249.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Prostasin regulates iNOS and cyclin D1 expression by modulating protease-activated receptor-2 signaling in prostate epithelial cells. AU - Chen,Li-Mei, AU - Hatfield,Meghan L, AU - Fu,Ya-Yuan, AU - Chai,Karl X, PY - 2009/8/12/entrez PY - 2009/8/12/pubmed PY - 2009/12/16/medline SP - 1790 EP - 801 JF - The Prostate JO - Prostate VL - 69 IS - 16 N2 - BACKGROUND: Prostasin is down-regulated during inflammation and in invasive cancers, and plays a role in regulation of inflammatory gene expression and invasion. METHODS: We used the human benign prostatic hyperplasia cell line BPH-1 to investigate gene expression changes associated with siRNA-mediated loss of prostasin expression. Quantitative PCR and/or western blotting were used to evaluate the expression changes of iNOS, ICAM-1, cyclin D1, IL-6, and IL-8. Gene expression changes were also evaluated in the presence of a PAR-2 antagonist. The PC-3 human prostate cancer cell line was used for evaluation of gene expression in response to prostasin re-expression. RESULTS: Prostasin silencing in BPH-1 was associated with up-regulation of iNOS, ICAM-1, IL-6, and IL-8, and down-regulation of cyclin D1; as well as reduced proliferation and invasion. The iNOS up-regulation and cyclin D1 down-regulation associated with prostasin silencing were inhibited by a PAR-2 antagonist. Re-expression of prostasin, a serine active-site mutant, and a GPI-anchor-free mutant, in the PC-3 cells resulted in PAR-2 and cyclin D1 transcription up-regulation. Transcription up-regulation of IL-6 and IL-8 was associated with re-expression of the serine active-site mutant prostasin in the PC-3 cells. Transcription up-regulation of IL-8, but to a lesser extent, was also observed in PC-3 cells expressing the wild-type prostasin. Expression of a serine protease active prostasin, GPI-anchored or anchor-free, prevented the IL-6 induction in response to PAR-2. The GPI-anchor-free prostasin also prevented the IL-8 induction. CONCLUSIONS: Prostasin plays a negative regulatory role on PAR-2-mediated signaling in prostate epithelial cells. SN - 1097-0045 UR - https://www.unboundmedicine.com/medline/citation/19670249/Prostasin_regulates_iNOS_and_cyclin_D1_expression_by_modulating_protease_activated_receptor_2_signaling_in_prostate_epithelial_cells_ L2 - https://doi.org/10.1002/pros.21030 DB - PRIME DP - Unbound Medicine ER -