TY - JOUR
T1 - Activation of nuclear factor-kappa B in human prostate carcinogenesis and association to biochemical relapse
AU - Domingo-Domenech, J.
AU - Mellado, B.
AU - Ferrer, B.
AU - Truan, D.
AU - Codony-Servat, J.
AU - Sauleda, S.
AU - Alcover, J.
AU - Campo, E.
AU - Gascon, P.
AU - Rovira, A.
AU - Ross, J.S.
AU - Fernández, P.L.
AU - Albanell, J.
PY - 2005
Y1 - 2005
N2 - Nuclear factor (NF)-kappa B/p65 regulates the transcription of a wide variety of genes involved in cell survival, invasion and metastasis. We characterised by immunohistochemistry the expression of NF-kappa B/p65 protein in six histologically normal prostate, 13 high-grade prostatic intraepithelial neoplasia (PIN) and 86 prostate adenocarcinoma specimens. Nuclear localisation of p65 was used as a measure of NF-kappa B active state. Nuclear localisation of NF-kappa B was only seen in scattered basal cells in normal prostate glands. Prostatic intraepithelial neoplasias exhibited diffuse and strong cytoplasmic staining but no nuclear staining. In prostate adenocarcinomas, cytoplasmic NF-kB was detected in 57 (66.3%) specimens, and nuclear NF-kappa B (activated) in 47 (54.7%). Nuclear and cytoplasmic NF-kappa B staining was not correlated (P = 0.19). By univariate analysis, nuclear localisation of NF-kappa B was associated with biochemical relapse (P = 0.0009; log- rank test) while cytoplasmic expression did not. On multivariate analysis, serum preoperative prostate specific antigen (P = 0.02), Gleason score (P = 0.03) and nuclear NF-kappa B (P = 0.002) were independent predictors of biochemical relapse. These results provide novel evidence for NF-kappa B/p65 nuclear translocation in the transition from PIN to prostate cancer. Our findings also indicate that nuclear localisation of NF-kappa B is an independent prognostic factor of biochemical relapse in prostate cancer.
AB - Nuclear factor (NF)-kappa B/p65 regulates the transcription of a wide variety of genes involved in cell survival, invasion and metastasis. We characterised by immunohistochemistry the expression of NF-kappa B/p65 protein in six histologically normal prostate, 13 high-grade prostatic intraepithelial neoplasia (PIN) and 86 prostate adenocarcinoma specimens. Nuclear localisation of p65 was used as a measure of NF-kappa B active state. Nuclear localisation of NF-kappa B was only seen in scattered basal cells in normal prostate glands. Prostatic intraepithelial neoplasias exhibited diffuse and strong cytoplasmic staining but no nuclear staining. In prostate adenocarcinomas, cytoplasmic NF-kB was detected in 57 (66.3%) specimens, and nuclear NF-kappa B (activated) in 47 (54.7%). Nuclear and cytoplasmic NF-kappa B staining was not correlated (P = 0.19). By univariate analysis, nuclear localisation of NF-kappa B was associated with biochemical relapse (P = 0.0009; log- rank test) while cytoplasmic expression did not. On multivariate analysis, serum preoperative prostate specific antigen (P = 0.02), Gleason score (P = 0.03) and nuclear NF-kappa B (P = 0.002) were independent predictors of biochemical relapse. These results provide novel evidence for NF-kappa B/p65 nuclear translocation in the transition from PIN to prostate cancer. Our findings also indicate that nuclear localisation of NF-kappa B is an independent prognostic factor of biochemical relapse in prostate cancer.
KW - prostate cancer
KW - NF-kappa B
KW - transcription factor
KW - malignant transformation
KW - PSA
KW - NECROSIS-FACTOR-ALPHA
KW - CANCER CELLS
KW - CONSTITUTIVE ACTIVATION
KW - INTRAEPITHELIAL NEOPLASIA
KW - INTERLEUKIN-6 EXPRESSION
KW - TRANSCRIPTION FACTOR
KW - CARCINOMA-CELLS
KW - KINASE-ALPHA
KW - APOPTOSIS
KW - INHIBITION
UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-27944434722&partnerID=MN8TOARS
U2 - 10.1038/sj.bjc.6602851
DO - 10.1038/sj.bjc.6602851
M3 - Article
SN - 0007-0920
VL - 93
SP - 1285
EP - 1294
JO - Br. J. Cancer
JF - Br. J. Cancer
ER -