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

Abstract

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.

Figure 1

Immunohistochemical detection of c-Rel (A–C), RelA (D–F), p50 (G–I), RelB (J–L), and p52 (M–O) in normal, PIN, and cancerous prostate tissues (× 400). Note nuclear RelB staining in a subset of normal glands (J). Also note a mixture of weak and strong p52 cytoplasmic staining in normal glands (M). Enlargements are provided to more clearly distinguish the subcellular localisation in cancer specimens.

Figure 2

Frequencies of NF-κB subunit combinations in the prostate cancer cores. The vertical pattern is for the canonical RelA–p50 pair. Noncanonical combinations are represented as follows: the diagonal pattern is for other class 1/class 2 dimers, and the dashed pattern is for class 1/class 1 or class 2/class 2 dimers. ^**P<0.01 χ² between RelA–p50 and RelA–RelB.