GLUCOCORTICOIDS INCREASE INSULIN-LIKE GROWTH FACTOR-II MESSENGER-RNA ACCUMULATION IN CULTURED HUMAN PHEOCHROMOCYTOMA CELLS

Human phaeochromocytomas abundantly express insulinlike growth factor- II (IGF-II), but its regulation and biological role in these neoplasms is not known at present. To clarify the regulation of IGF-II gene exp ression in phaeochromocytomas, we studied the effects of glucocorticoi ds, nerve growth factor (NGF), and protein kinase A and C regulators i n primary cultures of human phaeochromocytoma cells. Cytoplasmic RNA w as extracted and analysed by Northern and dot blotting with a P-32-lab elled cDNA probe for IGF-II. Dexamethasone treatment (500 ng/ml) for 3 and 7 days resulted in a 260% and 515% increase in the accumulation o f IGF-II mRNA respectively. The stimulatory effect of dexamethasone wa s time- and dose-dependent. The increases in the 6.0 and 2.2 kb specie s of IGF-II mRNAs were the most apparent. Cortisol (1 mu g/ml) increas ed the amount of IGF-II mRNA by threefold compared with the control. N GF (200 ng/ml), dibutyryl cyclic AMP (1 mM) and 12-O-tetradecanoyl pho rbol-13-acetate (a protein kinase C activator; 100 ng/ml) had no signi ficant effect on IGF-II mRNA levels. These data suggest that IGF-II ge ne expression in human phaeochromocytomas may be regulated by microenv ironmental glucocorticoids.