Lowered Amounts of the Tissue-specific Transcription Factor LFB1 (HNF1) Correlate with Decreased Levels of Glutathione S-Transferase α Messenger RNA in Human Renal Cell Carcinoma¹

Human renal cell carcinoma is characterized by the loss of differentiation markers such as glutathione S-transferase α (GST-α). In this paper we show that the promoter of a GST-α gene contains a functional binding site for the cell-specific transcription factor LFB1 (HNF1). To investigate the potential role of LFB1 in the down-regulation of GST-α expression, we have compared the amount and the binding activity of the LFB1 protein between normal kidney and tumor tissue. By Western analysis and gel retardation assay using a monoclonal antibody specific for LFB1 we show that in 11 of 14 carcinomas the amount of LFB1 is clearly reduced compared to the corresponding normal tissue and that in all 14 renal carcinomas LFB1 binding activity is diminished. As in the same samples the abundance of GST-α mRNA is lower than in the normal tissue, we postulate that the loss of LFB1 binding activity might be responsible for the decreased expression of the GST-α gene in renal cell carcinoma.