Increased activation of CCAAT/enhancer binding protein-beta correlates with the invasiveness of renal cell carcinoma.
Positive inflammatory reactions in an aggressive phenotype are typical features of renal cell carcinoma (RCC). Although a high blood level of inflammatory cytokines, such as interleukin-6, interleukin-8, and tumor necrosis factor-alpha, has been observed in these patients, the mechanisms underlying this clinical phenomenon remain to be elucidated. CCAAT/enhancer binding protein (C/EBP) family are transcription factors which play a role in cell differentiation and inflammatory reactions. Among these, C/EBP-beta induces a variety of cytokines and thus may play a role in the pathogenesis of RCC. We studied the activation of C/EBP-beta determined by electrophoretic mobility shift assay in nine RCC cell lines and 44 tissue samples. Six cell lines showed an activation of C/EBP-beta, whereas three cell lines did not, and two of these three had no expression at all of C/EBP-beta protein. Of 44 tissue samples, 12 (27.3%) showed a >200% increase in the activity compared with the corresponding normal kidney tissues. Locally advanced cases had a significantly higher rate of increased C/EBP-beta activity (5 of 8 = 62.5% in advanced cases versus 7 of 36 = 19.4% in localized cases). Especially, all four cases with renal vein invasion had an increased C/EBP-beta activity. These data suggest that the increased activation of C/EBP-beta may contribute to promote tumor invasiveness and render a malignant phenotype of RCC, although it needs to be validated in a larger series.
Oya
Mototsugu
M
Department of Urology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. moto-oya@sc.itc.keio.ac.jp
Horiguchi
Akio
A
Mizuno
Ryuichi
R
Marumo
Ken
K
Murai
Masaru
M
D000328:Adult; D000368:Aged; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism*; D002292:Carcinoma, Renal Cell / Q000473:pathology*; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D007249:Inflammation; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D007668:Kidney / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D010641:Phenotype; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D022782:CCAAT-Enhancer-Binding Protein-beta; D015850:Interleukin-6; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha