H19 AND INSULIN-LIKE GROWTH FACTOR-II GENE-EXPRESSION IN ADRENAL-TUMORS AND CULTURED ADRENAL-CELLS

The expression of H19 and insulin-like growth factor-II (IGF-LI) genes is important for fetal growth, and the misexpression of these genes m ay also be involved in the development of some tumors. In human fetal adrenals, H19 and IGF-II expression levels are very high. We show here that H19 is strongly expressed (similar to 50% of the expression in f etal adrenals and B-fold higher than that in adult liver) in normal ad ult adrenals (n = 9), adrenocortical adenomas (n = 28), and hyperplast ic adrenals (n = 11). In four hormonally active adrenocortical carcino mas, very low levels of H19 ribonucleic acid (RNA) were detected, wher eas IGF-II was highly expressed. In cultured adrenocortical cells, ACT H, (Bu)(2)cAMP, and cholera toxin increased H19 RNA accumulation 2- to 5-fold (P < 0.01), but had no significant effect on IGF-II messenger RNA levels. In pheochromocytomas (n = 22), H19 expression was variable , on the average, about 13% of the expression in the adjacent adrenal cortex. In primary cultures of pheochromocytoma cells, H19 RNA was not detectable via Northern blot analysis. Our data show that H19 express ion is maintained at high levels in adult human adrenals and benign ne oplasms. H19 RNA is up-regulated by ACTH in adult adrenocortical cells . The very low levels of H19 expression in hormonally active adrenocor tical carcinomas suggest that loss of H19 expression may be associated with malignancy in these neoplasms.