mRNA profiling of rat islet tumors reveals nkx 6.1 as a beta-cell-specific homeodomain transcription factor.

Jensen J, Serup P, Karlsen C, Nielsen TF, Madsen OD
J Biol Chem. 1996 271 (31): 18749-58

PMID: 8702531 · DOI:10.1074/jbc.271.31.18749

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.

MeSH Terms (22)

Adenoma, Islet Cell Animals Base Sequence Biomarkers DNA, Complementary DNA Primers Gene Expression Hexokinase Homeodomain Proteins Immunohistochemistry Islets of Langerhans Molecular Sequence Data Monosaccharide Transport Proteins Pancreatic Hormones Pancreatic Neoplasms Phenotype Polymerase Chain Reaction Rats Receptors, Cell Surface RNA, Messenger RNA, Neoplasm Transcription Factors

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