Glucocorticoids increase insulin-like growth factor-II mRNA accumulation in cultured human phaeochromocytoma cells.
Human phaeochromocytomas abundantly express insulin-like 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 expression in phaeochromocytomas, we studied the effects of glucocorticoids, nerve growth factor (NGF), and protein kinase A and C regulators in primary cultures of human phaeochromocytoma cells. Cytoplasmic RNA was extracted and analysed by Northern and dot blotting with a 32P-labelled 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 of IGF-II mRNA respectively. The stimulatory effect of dexamethasone was time- and dose-dependent. The increases in the 6.0 and 2.2 kb species of IGF-II mRNAs were the most apparent. Cortisol (1 microgram/ml) increased the amount of IGF-II mRNA by threefold compared with the control. NGF (200 ng/ml), dibutyryl cyclic AMP (1 mM) and 12-O-tetradecanoyl phorbol-13-acetate (a protein kinase C activator; 100 ng/ml) had no significant effect on IGF-II mRNA levels. These data suggest that IGF-II gene expression in human phaeochromocytomas may be regulated by microenvironmental glucocorticoids.
Department of Pathology, University of Helsinki, Finland.
J
J
Liu
A I
AI
Kahri
P
P
Heikkilä
W F
WF
Blum
R
R
Voutilainen
D000310:Adrenal Gland Neoplasms / Q000235:genetics / Q000378:metabolism*; D015152:Blotting, Northern; D003994:Bucladesine / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology; D007335:Insulin-Like Growth Factor II / Q000096:biosynthesis* / Q000235:genetics; D009414:Nerve Growth Factors / Q000494:pharmacology; D010673:Pheochromocytoma / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D009414:Nerve Growth Factors; D012333:RNA, Messenger; D003994:Bucladesine; D007335:Insulin-Like Growth Factor II; D003907:Dexamethasone; D013755:Tetradecanoylphorbol Acetate; D006854:Hydrocortisone