Differential expression of menin in various adrenal tumors. The role of menin in adrenal tumors.

Abstract

Adrenocortical tumors occur as sporadic tumors, as part of the multiple endocrine neoplasia type 1 (MEN1) syndrome, or as part of other hereditary disorders. MEN1 is a tumor suppressor gene located on chromosome 11q13 that encodes a 610-amino acid protein called menin, and plays an important role in the development of MEN1 syndrome. Recent reports indicate that heterozygous germline mutations of this gene are responsible for the disease onset of MEN1. To investigate the role of menin in sporadic adrenocortical tumors, the authors examined a series of adrenocortical adenoma cases and a single case of carcinoma and adrenomedulary tumors with the corresponding adjacent tumor tissues using reverse transcriptase-polymerase chain reaction (RT-PCR) for menin mRNA and Western blot analysis for menin protein. Both RNA and protein from these tumors were applied to RT-PCR and Western blot analysis, respectively, although they are not truly quantitative. Primers for RT-PCR were designed to amplify the sequence between exons 2 and 3 of the MEN1 gene. A specific antibody against menin was generated in guinea pigs immunized with the recombinant peptide from the amino acid residues 443-535 of menin made by using glutathione-S-transferase gene fusion. Based on the results of RT-PCR and Western blot analysis, both MEN1 mRNA and menin protein appeared to be highly expressed in Cushing syndrome resulting from adrenocortical adenomas and carcinoma. However, their expression was found to be greatly decreased in primary aldosteronism compared with their expression in Cushing syndrome. Although weak expression of MEN1 mRNA also was detected in pheochromocytoma on RT-PCR, menin expression was not detected in any case of pheochromocytoma by Western blot analysis, possibly due to the lower sensitivity of this assay compared with RT-PCR. Neither MEN1 mRNA nor menin protein was detected in any of the corresponding adjacent tumor tissues examined. The findings of the current study indicate that menin expression appears to be up-regulated in Cushing syndrome, suggesting that adrenocortical proliferation might be one of the primary lesions in the MEN1 syndrome in which menin might play a significant role in some specific cellular functions.