Molecular characterization of tumors from a transgenic mouse adrenal tumor model: Comparison with human pheochromocytoma

Abstract

Adrenal neuroblastoma and pheochromocytoma have the same embryonic origin from neural crest cells and mainly arise from the adrenal medulla. Recently, transgenic mice exhibiting tumors in the bilateral adrenal medulla by the expression of SV40 T-antigen were developed. In this study, we investigated mRNA expression in adrenal tumors of transgenic mice and compared them with human pheochromocytoma by DNA microarray analysis. To compare mouse adrenal tumors and human pheochromacytoma, we found that the expressions of noradrenergic neuron-related genes, including dopa decarboxylase, phenylethanolamine-N- methyltransferase and chromogranin B, were up-regulated in humans but not in mice; however, the expression of neuroblastoma-related genes, including Mycn, paired-like homeobox 2b, γ-aminobutyric acid A receptor β3 subunit, islet 1 and kinesin family member 1A, was up-regulated in both species. From the gene expression profiles, the characterization of mouse adrenal tumor, may be similar to that of human adrenal neuroblastoma rather than pheochromacytomas. This mouse model would be a useful tool for the development of anticancer drugs and for understanding the etiology of adrenal neuroblastoma.