Increased activation of CCAAT/enhancer binding protein-beta correlates with the invasiveness of renal cell carcinoma.

Abstract

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.