RGD Reference Report - Down-regulated CFTR During Aging Contributes to Benign Prostatic Hyperplasia. - Rat Genome Database

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Down-regulated CFTR During Aging Contributes to Benign Prostatic Hyperplasia.

Authors: Xie, C  Sun, X  Chen, J  Ng, CF  Lau, KM  Cai, Z  Jiang, X  Chan, HC 
Citation: Xie C, etal., J Cell Physiol. 2015 Aug;230(8):1906-15. doi: 10.1002/jcp.24921.
RGD ID: 11566048
Pubmed: PMID:25546515   (View Abstract at PubMed)
DOI: DOI:10.1002/jcp.24921   (Journal Full-text)

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-kappaB (NF-kappaB)/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-kappaB 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-kappaB inhibitor. More importantly, the involvement of CFTR in BPH was further demonstrated by the down-regulation of CFTR and up-regulation of COX2/NF-kappaB in human BPH samples. The present results suggest that CFTR may be involved in regulating PGE2 production through its negative regulation on NF-kappaB/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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
prostatic hypertrophy  IEP 11566048protein:decreased expression:prostate glandRGD 
prostatic hypertrophy  ISOCFTR (Homo sapiens)11566048; 11566048protein:decreased expression:prostate glandRGD 
prostatic hypertrophy  IEP 11566048; 11566048protein:increased expression:prostate glandRGD 
prostatic hypertrophy  ISOPTGS2 (Homo sapiens)11566048; 11566048protein:increased expression:prostate glandRGD 
prostatic hypertrophy  ISORELA (Homo sapiens)11566048; 11566048protein:increased expression:prostate glandRGD 

Objects Annotated

Genes (Rattus norvegicus)
Cftr  (CF transmembrane conductance regulator)
Ptgs2  (prostaglandin-endoperoxide synthase 2)
Rela  (RELA proto-oncogene, NF-kB subunit)

Genes (Mus musculus)
Cftr  (cystic fibrosis transmembrane conductance regulator)
Ptgs2  (prostaglandin-endoperoxide synthase 2)
Rela  (v-rel reticuloendotheliosis viral oncogene homolog A (avian))

Genes (Homo sapiens)
CFTR  (CF transmembrane conductance regulator)
PTGS2  (prostaglandin-endoperoxide synthase 2)
RELA  (RELA proto-oncogene, NF-kB subunit)


Additional Information