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

被引:121
作者
Lessard, L
Bégin, LR
Gleave, ME
Mes-Masson, AM
Saad, F
机构
[1] CHUM, Ctr Rech, Montreal, PQ H2L 4M1, Canada
[2] Univ Montreal, Inst Canc Montreal, Montreal, PQ H2L 4M1, Canada
[3] Hop Sacre Coeur, Serv Anatomopathol, Montreal, PQ H4J 1C5, Canada
[4] Univ British Columbia, Vancouver Gen Hosp, Prostate Ctr, Vancouver, BC V5Z 3J5, Canada
[5] Univ Montreal, Dept Med, Montreal, PQ H3C 3J7, Canada
[6] CHUM Notre Dame, Dept Chirurg Urol, Montreal, PQ H2L 4M1, Canada
关键词
prostate cancer; NF-kappa B; immunohistochemistry; tissue microarray; Gleason grade;
D O I
10.1038/sj.bjc.6602796
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Several reports suggest that the canonical nuclear factor-kappaB (NF-kappa B) pathway is constitutively activated in a subset of prostate cancer cells. However, except for RelA (p65), little is known about the status of NF-kappa B transcription factors in prostate cancer tissues. To clarify the status of NF-kappa B 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-kappa B 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-kappa B subunits in prostate cancer cells suggests for the first time that different NF-kappa B pathways and dimers may be activated in the progression of the disease.
引用
收藏
页码:1019 / 1023
页数:5
相关论文
共 27 条
[1]   Nuclear factor-κ-B:: The enemy within [J].
Aggarwal, BB .
CANCER CELL, 2004, 6 (03) :203-208
[2]   Growth and survival mechanisms associated with perineural invasion in prostate cancer [J].
Ayala, GE ;
Dai, H ;
Ittmann, M ;
Li, R ;
Powell, M ;
Frolov, A ;
Wheeler, TM ;
Thompson, TC ;
Rowley, D .
CANCER RESEARCH, 2004, 64 (17) :6082-6090
[3]   Control of oncogenesis and cancer therapy resistance by the transcription factor NF-κB [J].
Baldwin, AS .
JOURNAL OF CLINICAL INVESTIGATION, 2001, 107 (03) :241-246
[4]   Control of apoptosis by Rel/NF-κB transcription factors [J].
Barkett, M ;
Gilmore, TD .
ONCOGENE, 1999, 18 (49) :6910-6924
[5]   NF-κB activates prostate-specific antigen expression and is upregulated in androgen-independent prostate cancer [J].
Chen, CD ;
Sawyers, CL .
MOLECULAR AND CELLULAR BIOLOGY, 2002, 22 (08) :2862-2870
[6]   Selective activation of NF-κB subunits in human breast cancer:: potential roles for NF-κB2/p52 and for Bcl-3 [J].
Cogswell, PC ;
Guttridge, DC ;
Funkhouser, WK ;
Baldwin, AS .
ONCOGENE, 2000, 19 (09) :1123-1131
[7]   Regulation of major histocompatibility complex class I expression by NF-κB-related proteins in breast cancer cells [J].
Dejardin, E ;
Deregowski, V ;
Greimers, R ;
Cai, ZZ ;
Chouaib, S ;
Merville, MP ;
Bours, V .
ONCOGENE, 1998, 16 (25) :3299-3307
[8]   Nuclear factor-κB nuclear localization is predictive of biochemical recurrence in patients with positive margin prostate cancer [J].
Fradet, V ;
Lessard, L ;
Bégin, LR ;
Karakiewicz, P ;
Masson, AMM ;
Saad, F .
CLINICAL CANCER RESEARCH, 2004, 10 (24) :8460-8464
[9]  
Gasparian AV, 2002, J CELL SCI, V115, P141
[10]   Missing pieces in the NF-κB puzzle [J].
Ghosh, S ;
Karin, M .
CELL, 2002, 109 :S81-S96