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

• Published in: Cancer letters Vol. 106; no. 2; pp. 199 - 205
• Main Authors: Gu, H., Smith, M.W., Phelps, P.C., Berezesky, I.K., Merriman, R.L., Boder, G.B., Trump, B.F.
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 10.09.1996; Elsevier
• Subjects: Animals; Antineoplastic agents; Antineoplastic Agents - pharmacology; Biological and medical sciences; c-fos; c-jun; Calcium - metabolism; Cell Line; Cytosolic Ca 2; Egtazic Acid - pharmacology; Gene Expression Regulation - drug effects; General aspects; Genes, fos - drug effects; Genes, jun - drug effects; Genes, ras; H-ras; hsp-70; HSP70 Heat-Shock Proteins - genetics; Kidney - drug effects; Kidney - metabolism; Kidney cells; Medical sciences; Pharmacology. Drug treatments; Protein Kinase C - physiology; Protein kinases; Protein-Tyrosine Kinases - physiology; Rats; Sulfonylurea Compounds - pharmacology; Sulofenur; Transfection; c-jun; hsp-70; H-ras; Sulofenur; c-fos; Kidney cells; Cytosolic Ca 2; Protein kinases; Antineoplastic agent; Protein kinase C; Rat; Enzyme; Rodentia; Cytosol; In vitro; Kidney; Vertebrata; Mammalia; Calcium ion; Transfection; Animal; C-Onc gene; Established cell line; Heat shock protein; Sulfonylureas; Epithelial cell; Mechanism of action; Immediate early gene
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/0304-3835(96)04314-5

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 μM) treatment was greater in H/1.2NRK-52E. The maximum increases for NRK-2E and H/1.2NRK-52E were as follows: c-fos, ~10-fold and ~18-fold; c-jun, ~2.5-fold and ~3.6-fold; hsp70, ~13-fold and ~30-fold. In cells loaded with EGTA/AM or treated in low or no Ca 2+ 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,