Expression patterns of the c-myc gene in adrenocortical tumors and pheochromocytomas

Abstract

Abundant c-myc gene expression in neoplasms has been often linked to poor prognosis. As c-myc mRNA is expressed and hormonally regulated in human adrenals, we examined the c-myc gene expression in adrenal tumors by RNA analysis and immunohistochemistry to find out the possible role of c-myc in adrenal neoplasms. The abundant expression of the c-myc gene in normal adrenals was localized to the zona fasciculata and zona reticularis, with much lower expression in the zona glomerulosa and adrenal medulla. In hormonally active adrenocortical carcinomas (n = 6) and in virilizing adenomas (n = 4), c-myc mRNA levels were approximately 10% of those in normal adrenals (n = 11). In contrast, adrenal adenomas from patients with Cushing's (n = 4) and Conn's (n = 9) syndrome, non-functional adenomas (n = 2), adrenocortical hyperplasias (bilateral, n = 5; nodular, n = 4), and non-functional adrenocortical carcinomas (n = 3) expressed c-myc mRNA to the same extent as normal adrenals. The c-myc mRNA abundance in benign adrenal pheochromocytomas (n = 19) was similar to that in normal adrenal medulla. However, in malignant adrenal pheochromocytomas (n = 6), the average c-myc mRNA levels were approximately threefold that in benign adrenal pheochromocytomas. There was a good correlation between c-myc mRNA expression and immunohistochemical reactivity in both normal and pathological adrenal tissues. Southern blot analysis revealed no amplification or rearrangement of the c-myc gene in any of the adrenal tumors. In conclusion, c-myc expression localized to zona fasciculata and reticularis in normal adrenals. Virilizing adenomas and hormonally active adrenocortical carcinomas expressed c-myc mRNA clearly less than the other adrenal neoplasms and normal adrenal tissue. On the other hand, malignant pheochromocytomas contained more c-myc mRNA than benign ones. Further studies are required to clarify the mechanisms and significance for the distinct expression pattern of the c-myc gene in different adrenal neoplasms.

Influence of the high density lipoprotein receptor SR-BI on reproductive and cardiovascular pathophysiology

“…It also influences HDL's structure, cholesterol's delivery to and utilization by cells (including those in steroidogenic tissues), reproductive and cardiovascular physiology, and possibly other aspects of lipid metabolism (62). Because the in vitro activity, tissue distribution, and regulation of human SR-BI (34,(63)(64)(65) resemble those of the mouse, SR-BI may become an attractive target for prevention of or therapeutic intervention in a variety of human diseases (13,17,18,22,23).…”

Inhibition of DNA methylation increases follistatin expression and secretion in the human adrenocortical cell line NCI-H295R

“…Shortly, genomic DNA was isolated (Liu et al 1997) and DNA was then digested for 6 h with HpaII/MspI enzymes (Roche Molecular Biochemicals) according to the manufacturer's recommendations. The PCR reactions were performed in 20 µl containing 0·2 µM of each dNTP, 1 reaction buffer, 1·75 mM MgCl 2, 1·3% DMSO, 0·5 µM forward and reverse primers, 1·5 U Taq DNA polymerase (Fermentas, Tamro Corporation, Vantaa, Finland) and 50 ng of template DNA.…”

cAMP-dependent protein kinase activation inhibits proliferation and enhances apoptotic effect of tumor necrosis factor-α in NCI-H295R adrenocortical cells

“…For clarifying the potential mechanisms underlying the synergistic effects of TNF and (Bu) 2 cAMP on apoptosis, we compared c-myc gene expression in H295R, SW-13, Y-1 and HeLa cells, since our previous studies showed that c-myc expression was upregulated by (Bu) 2 cAMP in primary cultures of normal human adrenal cells and was lost in adrenocortical carcinomas (Liu et al 1996b(Liu et al , 1997.…”

“…We previously found that ACTH is able to induce differentiation and apoptosis, but it inhibits proliferation of rat fetal adrenocortical cells in primary cultures (Arola et al 1993). Expression of the proto-oncogene c-myc gene is lost in human adrenocortical carcinomas (Liu et al 1997) and induction of c-myc expression by PKA activation is observed during ACTH treatment in primary cultures of human adrenocortical cells (Liu et al 1996b). In many cell types, induction of c-myc expression puts the cells on the crossroads of coupled pathways: it promotes cell cycle progression, inhibits cell differentiation and sensitizes the cells to apoptosis (Pelengaris et al 2002).…”