Nuclear localisation of nuclear factor-kappaB transcription factors in prostate cancer: an immunohistochemical study

• Published in: British journal of cancer Vol. 93; no. 9; pp. 1019 - 1023
• Main Authors: LESSARD, L, BEGIN, L. R, GLEAVE, M. E, MES-MASSON, A.-M, SAAD, F
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 31-10-2005
• Subjects: Adenocarcinoma - metabolism; Adenocarcinoma - pathology; Apoptosis; Biological and medical sciences; Cancer research; Cancer therapies; Cell Nucleus - metabolism; Dimerization; Disease Progression; DNA-Binding Proteins - metabolism; Humans; Immunoenzyme Techniques; Kinases; Localization; Male; Medical research; Medical sciences; Molecular Diagnostics; Nephrology. Urinary tract diseases; NF-kappa B - metabolism; NF-kappa B p50 Subunit - metabolism; NF-kappa B p52 Subunit - metabolism; Nuclear Proteins - metabolism; Prostate cancer; Prostate-Specific Antigen - metabolism; Prostatic Intraepithelial Neoplasia - metabolism; Prostatic Intraepithelial Neoplasia - pathology; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - pathology; Proteins; Proto-Oncogene Proteins c-rel; Subcellular Fractions; Tissue Array Analysis; Transcription Factor RelA - metabolism; Transcription Factor RelB - metabolism; Transcription Factors; Tumors; Tumors of the urinary system; Urinary tract. Prostate gland; Canada; Montreal Quebec Canada; Quebec Canada; Immunohistochemistry; Urinary system disease; Prostate disease; Gleason grade; Malignant tumor; Signal transduction; NF-κB; Anatomic pathology; Cancerology; Tissue microarrays; Transcription factor NFκB; Tissue Microarray; Transcription factor; Male genital diseases; Prostate cancer
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/sj.bjc.6602796

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.