LOWERED AMOUNTS OF THE TISSUE-SPECIFIC TRANSCRIPTION FACTOR LFB1 (HNF1) CORRELATE WITH DECREASED LEVELS OF GLUTATHIONE-S-TRANSFERASE ALPHA-MESSENGER-RNA IN HUMAN RENAL-CELL CARCINOMA

Human renal cell carcinoma is characterized by the loss of differentia tion markers such as glutathione S-transferase alpha (GST-alpha). In t his paper we show that the promoter of a GST-alpha gene contains a fun ctional binding site for the cell-specific transcription factor LFB1 ( HNF1). To investigate the potential role of LFB1 in the down-regulatio n of GST-alpha 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 antib ody specific for LFB1 we show that in 11 of 14 carcinomas the amount o f LFB1 is clearly reduced compared to the corresponding normal tissue and that in all 14 renal carcinomas LFB1 binding activity is diminishe d. As in the same samples the abundance of GST-alpha mRNA is lower tha n in the normal tissue, we postulate that the loss of LFB1 binding act ivity might be responsible for the decreased expression of the GST-alp ha gene in renal cell carcinoma.