HUMAN RENAL-CELL CARCINOGENESIS IS ACCOMPANIED BY A COORDINATE LOSS OF THE TISSUE-SPECIFIC TRANSCRIPTION FACTORS HNF4-ALPHA AND HNF1-ALPHA

Human renal cell carcinogenesis is usually accompanied by dedifferenti ation processes including the loss of expression of tissue specificall y expressed genes. Based on the hypothesis that these dedifferentiatio n processes might be attributed to a functional change in tissue speci fic transcription factors, we have analyzed the expression and functio n of the tissue specific transcription factor HNF4 alpha in human rena l cell carcinomas. By Western blot analysis and gel retardation assay using HNF4 alpha specific antibodies, we observed that in most cases t he amount as well as the binding activity of HNF4 is reduced in the tu mor samples compared to the corresponding normal tissues. Furthermore, we found a clear correlation between the HNF4 alpha binding activity and the amount of another transcription factor (HNF1 alpha), which is thought to be transcriptionally activated by HNF4 alpha. We therefore speculate that disruption of the HNF4 alpha/HNF1 alpha pathway of kidn ey specific gene expression might be an important molecular mechanism in renal cell carcinogenesis.