EFFECTS OF PAX2 EXPRESSION IN A HUMAN FETAL KIDNEY (HEK293) CELL-LINE

PAX2, a member of the ''paired-box'' family of homeotic genes, is a nu clear transcription factor expressed in the early stages of nephrogene sis by induced blastemal cells as they progress from mesenchymal conde nsates to the ''S-shaped'' stage and also by the ureteric bud. Spontan eous mutations in one copy of PAX2 in humans causes a syndrome of prot einuric renal failure and coloboma of the eye (P. Sanyanusin et al., N at. Genet. 9 (1995) 358-363); transgenic mice with disruption of the P AX2 gene are anephric (M. Torres et al., Development 121 (1995) 4057-4 067. Although PAX2 is clearly critical for normal kidney development, its direct effects on kidney cell phenotype are unknown. To address th is issue, we developed stable transfectants of the HEK293 human fetal kidney epithelial cell line expressing human PAX2 protein under tetrac ycline-regulatable promoter. In these cells, PAX2 had no effect on the proliferative rate, but increased the expression of the Wilms' tumor gene (2-fold) and E-cadherin (7-fold). PAX2 had a strong inhibitory ef fect on vimentin; vimentin/GAPDH mRNA ratio was suppressed to 8% of co ntrol whereas cytokeratin-18/GAPDH mRNA ratio was unchanged. During ne phrogenesis, loss of vimentin and onset of low-level WT1 and E-cadheri n expression occur in mesenchymal condensates. Our observations sugges t that these events may be, in part, regulated by PAX2. (C) 1998 Elsev ier Science B.V.