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 the immediate-early genes (IEG) c-Fos and c-Jun and the stress gene HSP70 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 induction for each gene after sulofenur (500 microM) treatment was greater in H/1.2NRK-52E. The maximum increases for NRK-2E and H/1.2NRK-52E were as follows: c-Fos, approximately 10-fold and approximately 18-fold; c-Jun, approximately 2.5-fold and approximately 3.6-fold; HSP70, approximately 13-fold and approximately 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 types. However, inhibition of protein kinases with staurosporin and calphostin 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-ras-transfected cells.