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Åke Lernmark

Principal investigator

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

Author

  • O. D. Madsen
  • L. C. Andersen
  • B. Michelsen
  • D. Owerbach
  • L. I. Larsson
  • A. Lernmark
  • D. F. Steiner

Summary, in English

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.

Publishing year

1988-01-01

Language

English

Pages

6652-6656

Publication/Series

Proceedings of the National Academy of Sciences of the United States of America

Volume

85

Issue

18

Document type

Journal article

Publisher

National Acad Sciences

Topic

  • Cell and Molecular Biology

Status

Published

ISBN/ISSN/Other

  • ISSN: 0027-8424