Tissue-specific expression of transfected human insulin genes in pluripotent clonal rat insulinoma lines induced during passage in vivo

Research output: Contribution to journalArticle

Abstract

The pluripotent rat islet tumor cell line MSL-G2 expresses primarily glucagon or cholecystokinin and not insulin in vitro but changes phenotype completely after prolonged in vivo cultivation to yield small-sized hypoglycemic tumors composed almost entirely of insulin-producing beta cells. When a genomic DNA fragment containing the coding and upstream regulatory regions of the human insulin gene was stably transfected into MSL-G2 cells no measurably amounts of insulin or insulin mRNA were detected in vitro. However, successive transplantation of two transfected clones resulted in hypoglycemic tumors that efficiently coexpressed human and rat insulin as determined by human C-peptide-specific immunoreagents. These results demonstrate that cis-acting tissue-specific insulin gene enhancer elements are conserved between rat and human insulin genes. We propose that the in vivo differentiation of MSL-G2 cells and transfected subclones into insulin-producing cells reflects processes of natural beta-cell ontogeny leading to insulin gene expression.

Details

Authors
  • O. D. Madsen
  • L. C. Andersen
  • B. Michelsen
  • D. Owerbach
  • L. I. Larsson
  • A. Lernmark
  • D. F. Steiner
External organisations
  • Hagedorn Research Institute
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cell and Molecular Biology
Original languageEnglish
Pages (from-to)6652-6656
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume85
Issue number18
Publication statusPublished - 1988 Jan 1
Publication categoryResearch
Peer-reviewedYes
Externally publishedYes