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.
Gu
H
H
Department of Pathology, University of Maryland School of Medicine, Baltimore 21201, USA.
Smith
M W
MW
Phelps
P C
PC
Berezesky
I K
IK
Merriman
R L
RL
Boder
G B
GB
Trump
B F
BF
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D004533:Egtazic Acid / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D016762:Genes, fos / Q000187:drug effects*; D016758:Genes, jun / Q000187:drug effects*; D011905:Genes, ras; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D011493:Protein Kinase C / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D051381:Rats; D013453:Sulfonylurea Compounds / Q000494:pharmacology*; D014162:Transfection
D000970:Antineoplastic Agents; D018840:HSP70 Heat-Shock Proteins; D013453:Sulfonylurea Compounds; D004533:Egtazic Acid; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C; D002118:Calcium; C058179:sulofenur