PMID:25546515

Citation	Xie, C, Sun, X, Chen, J, Ng, CF, Lau, KM, Cai, Z, Jiang, X and Chan, HC (2015) Down-regulated CFTR During Aging Contributes to Benign Prostatic Hyperplasia. J. Cell. Physiol. 230:1906-15
Abstract	Benign prostatic hyperplasia (BPH) is a hyper-proliferative disease of the aging prostate; however, the exact mechanism underlying the development of BPH remains incompletely understood. The present study investigated the possible involvement of the cystic fibrosis transmembrane conductance regulator (CFTR), which has been previously shown to negatively regulate nuclear factor-κB (NF-κB)/cyclooxygenase 2 (COX2)/prostaglandin E2 (PGE2) pathway, in the pathogenesis of BPH. Our results showed decreasing CFTR and increasing COX2 expression in rat prostate tissues with aging. Furthermore, suppression of CFTR led to increased expression of COX2 and over-production of PGE2 in a normal human prostate epithelial cell line (PNT1A) with elevated NF-κB activity. PGE2 stimulated the proliferation of primary rat prostate stromal cells but not epithelial cells, with increased PCNA expression. In addition, the condition medium from PNT1A cells after inhibition or knockdown of CFTR promoted cell proliferation of prostate stromal cells which could be reversed by COX2 or NF-κB inhibitor. More importantly, the involvement of CFTR in BPH was further demonstrated by the down-regulation of CFTR and up-regulation of COX2/NF-κB in human BPH samples. The present results suggest that CFTR may be involved in regulating PGE2 production through its negative regulation on NF-κB/COX2 pathway in prostate epithelial cells, which consequently stimulates cell growth of prostate stromal cells. The overstimulation of prostate stromal cell proliferation by down-regulation of CFTR-enhanced PGE2 production and release during aging may contribute to the development of BPH.
Links	PubMed Online version:10.1002/jcp.24921
Keywords	Aging/metabolism; Animals; Blotting, Western; Cell Line, Tumor; Cyclooxygenase 2/metabolism; Cystic Fibrosis Transmembrane Conductance Regulator/biosynthesis; Dinoprostone/biosynthesis; Disease Models, Animal; Down-Regulation; Fluorescent Antibody Technique; Humans; Immunohistochemistry; Male; NF-kappa B/metabolism; Prostatic Hyperplasia/metabolism; Rats; Rats, Sprague-Dawley; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction/physiology; Transfection
edit table

Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
RAT:CFTR	involved_in	GO:0007568: aging	ECO:0000270: expression pattern evidence used in manual assertion		P		Seeded From UniProt	complete

References

See Help:References for how to manage references in GONUTS.