Human renal cell carcinogenesis is accompanied by a coordinate loss of the tissue specific transcription factors HNF4α and HNF1α

Human renal cell carcinogenesis is usually accompanied by dedifferentiation processes including the loss of expression of tissue specifically expressed genes. Based on the hypothesis that these dedifferentiation processes might be attributed to a functional change in tissue specific transcription factors, we have analyzed the expression and function of the tissue specific transcription factor HNF4α in human renal cell carcinomas. By Western blot analysis and gel retardation assay using HNF4α specific antibodies, we observed that in most cases the amount as well as the binding activity of HNF4 is reduced in the tumor samples compared to the corresponding normal tissues. Furthermore, we found a clear correlation between the HNF4α binding activity and the amount of another transcription factor (HNF1α), which is thought to be transcriptionally activated by HNF4α. We therefore speculate that disruption of the HNF4α/HNF1α pathway of kidney specific gene expression might be an important molecular mechanism in renal cell carcinogenesis.