Nuclear localisation of nuclear factor-kappaB transcription factors in prostate cancer: an immunohistochemical study.
Several reports suggest that the canonical nuclear factor-kappaB (NF-kappaB) pathway is constitutively activated in a subset of prostate cancer cells. However, except for RelA (p65), little is known about the status of NF-kappaB transcription factors in prostate cancer tissues. To clarify the status of NF-kappaB subunits, we analysed the expression and subcellular localisation of RelA, RelB, c-Rel, p50, and p52 on tissue array sections containing respectively 344, 346, 369, 343, and 344 cores from 75 patients. The subcellular localisation of NF-kappaB factors was tested against relevant clinical parameters (preoperative prostate-specific antigen, pathological stage, and postoperative Gleason grade). With the exception of c-Rel, each subunit was detected in the nucleus of cancer cells: significant nuclear expression of RelB, RelA, p52, and p50 was seen in 26.6, 15.6, 10.7, and 10.5% of cores, respectively. Surprisingly, cores expressing both nuclear RelA and p50 canonical pathway proteins were less frequently observed than cores expressing other subunit combinations such as RelB-p52 and RelA-RelB. In addition, the nuclear localisation of RelB correlated with patient's Gleason scores (Spearman correlation: 0.167; P=0.018). The nuclear localisation of both canonical and noncanonical NF-kappaB subunits in prostate cancer cells suggests for the first time that different NF-kappaB pathways and dimers may be activated in the progression of the disease.
Lessard
L
L
Centre de recherche du CHUM, and Institut du cancer de Montréal, 1560 Sherbrooke Est, Montréal, Québec, Canada H2L 4M1.
Bégin
L R
LR
Gleave
M E
ME
Mes-Masson
A-M
AM
Saad
F
F
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D002467:Cell Nucleus / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D019281:Dimerization; D018450:Disease Progression; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D052002:NF-kappa B p50 Subunit / Q000378:metabolism; D052003:NF-kappa B p52 Subunit / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D017430:Prostate-Specific Antigen / Q000378:metabolism; D019048:Prostatic Intraepithelial Neoplasia / Q000378:metabolism* / Q000473:pathology; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D020569:Proto-Oncogene Proteins c-rel; D013347:Subcellular Fractions; D046888:Tissue Array Analysis; D051996:Transcription Factor RelA / Q000378:metabolism; D051841:Transcription Factor RelB / Q000378:metabolism; D014157:Transcription Factors
D004268:DNA-Binding Proteins; D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; D052003:NF-kappa B p52 Subunit; D009687:Nuclear Proteins; D020569:Proto-Oncogene Proteins c-rel; C068059:REL protein, human; C498143:RELA protein, human; C497593:RELB protein, human; D051996:Transcription Factor RelA; D014157:Transcription Factors; D051841:Transcription Factor RelB; D017430:Prostate-Specific Antigen