Regulation of neuropeptide Y mRNA expression in cultured human pheochromocytoma cells

The expression of the neuropeptide Y (NPY) gene caries considerably in huma n pheochromocytomas, but the mechanisms for this variation have not been cl arified. To investigate the regulation pattern of the NPY gene in human phe ochromocytomas, we screened 16 pheochromocytomas and 9 normal adrenal tissu es with Northern blots. The expression level of NPY mRNA in normal adrenal medulla was low and relatively constant, while the pheochromocytomas showed a very wide variation in NPY mRNA levels in both malignant and benign tumo rs. This indicates that NPY gene expression is not correlated with malignan cy in pheochromocytomas. In primary cultures of human pheochromocytoma cell s, nerve growth factor treatment (causing neuronal differentiation) increas ed NPY mRNA accumulation 2- to 5-fold (P< 0.05). NPY mRNA levels were also induced by protein kinase modulators (Bu)(2)cAMP and staurosporine in the c ultures (P < 0.05). In contrast, treatment with dexamethasone and IGF-II (c ausing or linked with chromaffin differentiation) reduced NPY mRNA accumula tion (P < 0.05). These data show that the regulation pattern of NPY mRNA ex pression in cultured human pheochromocytoma cells is different from that pr eviously described in rat pheochromocytoma PC12 cells. Regulation of NPY mR NA expression in primary cultures by these differentiating factors suggests that the expression of NPY mRNA in pheochromocytoma tissues may be associa ted with the neuronal differentiation of the tumor cells affected by multip le factors.