H-RAS TRANSFECTION OF THE RAT-KIDNEY CELL-LINE NRK-52E RESULTS IN INCREASED INDUCTION OF C-FOS, C-JUN AND HSP70 FOLLOWING SULOFENUR TREATMENT

The effect of the antineoplastic drug sulofenur on the induction of th e immediate-early genes (IEG) c-fos and c-jun and the stress gene hsp7 0 was compared in the rat kidney epithelial-like cell line NRK-52E and a derivative H-ras-transfected (H/1.2NRK-52E) cell line. Fold inducti on for each gene after sulofenur (500 mu M) treatment was greater in H /1.2NRK-52E. The maximum increases for NRK-2E and H/1.2NRK-52E were as follows: c-fos, similar to 10-fold and similar to 18-fold; c-jun, sim ilar to 2.5-fold and similar to 3.6-fold; hsp70,similar to 13-fold and similar to 30-fold. In cells loaded with EGTA/AM or treated in low or no Ca2+ HBSS, c-fos induction was reduced similarly in both cell type s. However, inhibition of protein kinases with staurosporin and calpho stin C reduced c-fos by 80% in NRK-52E but by only 10-20% in H/1.2NRK- 52E. These results indicate that sulofenur-induced IEG elevation is Ca 2+-dependent and that the requirement for protein kinase C activation is bypassed in H-ms-transfected cells.