Immunohistochemical analysis of NF-kappaB signaling proteins IKKepsilon, p50/p105, p52/p100 and RelA in prostate cancers.
Activation of nuclear factor-kappa B (NF-kappaB) signaling is considered an important mechanism in the development of prostate cancers. A recent study revealed that IkappaB kinase epsilon (IKKepsilon), an activator of NF-kappaB, was overexpressed in breast cancers and acted as an oncogene. Expression of NF-kappaB members has been reported in prostate cancer tissues, but expression of IKKepsilon has not yet been studied in prostate cancers. In this study, we attempted to explore as to whether expressions of IKKepsilon and NF-kappaB members p50/105, p52/p100 and RelA are altered in prostate cancers. We analyzed the expression of IKKepsilon, p50/105, p52/p100 and RelA in 107 prostate adenocarcinoma tissues by immunohistochemistry using a tissue microarray (TMA) method. In the TMA, IKKepsilon is expressed in basal cells, but not in alveolar cells in normal prostate glands. IKKepsilon is expressed in 60.0% of prostate intraepithelial neoplasm (PIN) and 70.1% of the prostate cancers in the cytoplasm. Nuclear immunostainings of NF-kappaB members p50/105, p52/p100 and RelA, which are considered activation of NF-kappaB signaling, were observed respectively in 28.0%, 18.7% and 37.4% of the cancers. Nuclear staining was detected neither in normal alveolar cells nor in PIN. However, none of the expression of p50/105 nor p52/p100 nor RelA nor IKKepsilon was associated with pathologic characteristics, including size of the cancers, age, Gleason score and stage. The increased cytoplasmic expression of IKKepsilon as well as the increased nuclear expressions of p50/105, p52/p100 and RelA in the prostate cancers compared to normal alveolar cells suggested that overexpression of these proteins may be related to activation of the NF-kappaB pathway and might play a role in tumorigenesis of prostate cancers.
Seo
Seong Il
SI
Department of Urology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Song
Sang Yong
SY
Kang
Mi Ran
MR
Kim
Min Sung
MS
Oh
Ji Eun
JE
Kim
Yoo Ri
YR
Lee
Ji Youl
JY
Yoo
Nam Jin
NJ
Lee
Sug Hyung
SH
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000328:Adult; D000368:Aged; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051550:I-kappa B Kinase / Q000032:analysis / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D052002:NF-kappa B p50 Subunit / Q000032:analysis / Q000096:biosynthesis*; D052003:NF-kappa B p52 Subunit / Q000032:analysis / Q000096:biosynthesis*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D015398:Signal Transduction; D046888:Tissue Array Analysis; D051996:Transcription Factor RelA / Q000032:analysis / Q000096:biosynthesis*
D052002:NF-kappa B p50 Subunit; D052003:NF-kappa B p52 Subunit; D051996:Transcription Factor RelA; D051550:I-kappa B Kinase