The MEN-1 Gene Is Rarely Down-Regulated in Pituitary Adenomas

Publisher Website
Google Scholar
Abstract
The gene for multiple endocrine neoplasia type 1 (MEN-1) has recently been cloned and encodes a putative tumor suppressor protein named menin. We have previously reported inactivating MEN-1 gene mutations associated with loss of heterozygosity (LOH) of the normal allele in tumors of patients with MEN-1 and in some sporadic pituitary tumors. These genetic alterations, how- ever, are noted in no more than 10% of sporadic adenomas. To investigate whether other mechanisms may result in down-regu- lation of menin gene expression in pituitary adenomas, we exam- ined menin gene expression by semiquantitative RT-PCR in 60 sporadic pituitary adenomas. Ribonucleic acid (RNA) was ex- tracted from surgically resected, morphologically characterized tu- mors. Primers were designed to amplify a 257-bp fragment span- ning exons 4 - 6 of the MEN-1 gene. A product of the predicted size was amplified from normal pituitary samples as well as from ad- enomas. Competitive PCR was performed with the housekeeping gene PGK-1 to quantitate menin gene expression. A comparable ratio of menin/PGK-1 messenger RNA was identified in all but three samples; in two tumors with LOH, menin expression was weak, and in one tumor, menin messenger RNA was undetectable, associated with LOH and mutation of the other allele. Reduced expression of menin in some sporadic adenomas is con- sistent with a putative tumor suppressor role for this gene product. However, lack of menin down-regulation in the majority of these tumors, which exhibit LOH at 11q13 in up to 20% of cases, provides compelling evidence for an additional tumor suppressor gene at this locus, which is more commonly involved in the pathogenesis of pitu- itary neoplasms. (J Clin Endocrinol Metab 83: 3210 -3212, 1998)

This publication has 0 references indexed in Scilit: