In situ analysis of human menin in normal and neoplastic pancreatic tissues: evidence for differential expression in exocrine and endocrine cells.
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.
Cavallari
Ilaria
I
Department of Oncology and Surgical Sciences, University of Padova, I-35128 Padova, Italy.
D'Agostino
Donna M
DM
Ferro
Tiziana
T
Rosato
Antonio
A
Barzon
Luisa
L
Pasquali
Claudio
C
Fogar
Paola
P
Theodoropoulou
Marily
M
Esposito
Giovanni
G
Boscaro
Marco
M
Pagotto
Uberto
U
Tebaldi
Elisabetta
E
Fallo
Francesco
F
Chieco-Bianchi
Luigi
L
Ciminale
Vincenzo
V
D000368:Aged; D000911:Antibodies, Monoclonal; D004247:DNA / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D019084:Fluorescent Antibody Technique, Indirect; D015408:Gastrinoma / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D007340:Insulinoma / Q000378:metabolism; D007515:Islets of Langerhans / Q000166:cytology / Q000378:metabolism*; D008297:Male; D018613:Microscopy, Confocal; D009363:Neoplasm Proteins / Q000032:analysis* / Q000235:genetics; D010179:Pancreas / Q000166:cytology / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D011518:Proto-Oncogene Proteins
D000911:Antibodies, Monoclonal; C105373:MEN1 protein, human; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D004247:DNA