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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.

Pubmed ID: 8702531


  • Jensen J
  • Serup P
  • Karlsen C
  • Nielsen TF
  • Madsen OD


The Journal of biological chemistry

Publication Data

August 2, 1996

Associated Grants


Mesh Terms

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