Cavallari Ilaria, D'Agostino Donna M, Ferro Tiziana, Rosato Antonio, Barzon Luisa, Pasquali Claudio, Fogar Paola, Theodoropoulou Marily, Esposito Giovanni, Boscaro Marco, Pagotto Uberto, Tebaldi Elisabetta, Fallo Francesco, Chieco-Bianchi Luigi, Ciminale Vincenzo
Department of Oncology and Surgical Sciences, University of Padova, I-35128 Padova, Italy.
J Clin Endocrinol Metab. 2003 Aug;88(8):3893-901. doi: 10.1210/jc.2002-021840.
Multiple endocrine neoplasia type 1 (MEN1) is a hereditary syndrome linked to mutations in the MEN1 gene, which encodes a 610-amino-acid nuclear protein termed menin. Because of the lack of a suitable detection protocol, the in situ expression pattern of menin in human tissues remains to be determined. In this study, we have developed an antimenin monoclonal antibody and an indirect immunofluorescence/laser-scanning microscopy protocol for analyzing menin expression in frozen tissue sections. Because neuroendocrine pancreatic tumors represent a key feature of MEN1, we focused this study on nontumoral pancreas and a small panel of neuroendocrine pancreatic tumors. Results showed that menin was readily detected in nontumoral exocrine cells. In contrast, most islet cells expressing insulin, glucagon, or somatostatin showed considerably weaker levels of menin expression; however, a subpopulation of pancreatic polypeptide-positive cells exhibited a signal comparable with that detected in adjacent exocrine cells. Sporadic endocrine tumors showed variable levels of menin expression, whereas a MEN1-/- gastrinoma scored negative. This report thus provides the first description of the expression pattern of menin in human pancreas in situ and lays the groundwork for further studies of other tissues and tumors.
1型多发性内分泌腺瘤病（MEN1）是一种与MEN1基因突变相关的遗传性综合征，该基因编码一种名为menin的含610个氨基酸的核蛋白。由于缺乏适当的检测方案，menin在人体组织中的原位表达模式仍有待确定。在本研究中，我们开发了一种抗menin单克隆抗体和一种间接免疫荧光/激光扫描显微镜检测方案，用于分析menin在冷冻组织切片中的表达。由于神经内分泌胰腺肿瘤是MEN1的一个关键特征，我们将这项研究的重点放在非肿瘤性胰腺和一小部分神经内分泌胰腺肿瘤上。结果显示，在非肿瘤性外分泌细胞中很容易检测到menin。相比之下，大多数表达胰岛素、胰高血糖素或生长抑素的胰岛细胞中menin的表达水平明显较弱；然而，一小部分胰腺多肽阳性细胞显示出与相邻外分泌细胞中检测到的信号相当的信号。散发性内分泌肿瘤中menin的表达水平各不相同，而1型多发性内分泌腺瘤病基因敲除（MEN1-/-）的胃泌素瘤检测结果为阴性。因此，本报告首次描述了menin在人体胰腺中的原位表达模式，并为进一步研究其他组织和肿瘤奠定了基础。
