mRNA profiling of rat islet tumors reveals nkx 6.1 as a beta-cell-specific homeodomain transcription factor.
Development of a high capacity multiplex reverse transcriptase-polymerase chain reaction protocol has allowed us to screen lineage related rat islet tumors classified as alpha-, beta-, and delta-like as judged by their hormone profile for differential expression of more than 50 selected genes. We find that in addition to insulin the insulinoma express the normal beta-cell markers Pdx-1, IAPP, and Glut-2, and that these markers are absent from the glucagonoma: a reflection of the normal alpha-cell. Furthermore, this study suggests that the GLP-1, glucagon, GIP, IGF-1, and insulin receptors as well as E-cadherin, R-cadherin, Id-1, and Id-2 are differentially expressed within the islet of Langerhans. Importantly, insulinoma-specific expression of the recently cloned homeodomain protein Nkx 6.1 predicted beta-cell-specific expression in the normal islet. Immunohistochemistry using antibodies raised against recombinant Nkx 6.1 did indeed localize Nkx 6.1 expression exclusively to the nuclei of normal islet beta-cells. Apart from pancreatic islets only the antral part of the stomach contained Nkx 6.1 mRNA. We conclude that multiplex reverse transcriptase-polymerase chain reaction-based mRNA profiling is a powerful tool to identify differentially expressed genes within phenotypically related cells and propose that Nkx 6.1 is involved in specifying the unique characteristics of the beta-cell.
Jensen
J
J
Hagedorn Research Institute, Niels Steensensvej 6, DK-2820 Gentofte, Denmark.
Serup
P
P
Karlsen
C
C
Nielsen
T F
TF
Madsen
O D
OD
D007516:Adenoma, Islet Cell / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D015415:Biomarkers; D017931:DNA Primers / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D015870:Gene Expression; D006593:Hexokinase / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D007150:Immunohistochemistry; D007515:Islets of Langerhans / Q000378:metabolism*; D008969:Molecular Sequence Data; D009004:Monosaccharide Transport Proteins / Q000235:genetics; D010187:Pancreatic Hormones / Q000235:genetics; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D011956:Receptors, Cell Surface / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
D015415:Biomarkers; D017931:DNA Primers; D018076:DNA, Complementary; D018398:Homeodomain Proteins; D009004:Monosaccharide Transport Proteins; D010187:Pancreatic Hormones; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011956:Receptors, Cell Surface; D014157:Transcription Factors; D006593:Hexokinase