Diet-dependent carcinogenesis of pancreatic islets and liver in transgenic mice expressing oncogenes under the control of the L-type pyruvate kinase gene promoter

Oncogene. 1992 Jul;7(7):1413-22.


The liver-type pyruvate kinase (L-PK) gene is controlled positively by insulin and carbohydrates, negatively by glucagon and fasting. Diet-inducible models of carcinogenesis were obtained using the L-PK gene promoter and regulatory sequences to control the expression of c-myc and SV40 T oncogenes in transgenic mice. L-PK/c-myc and L-PK/Tag animals fed a carbohydrate-rich diet developed hepatocarcinomas. In addition, L-PK/Tag animals developed diet-dependent, aggressive endocrine pancreatic tumors, preceded by islet hyperplasia involving the different analysed cell populations (alpha, beta and delta). Expression of the L-PK gene was demonstrated in pancreatic tumors, in rat isolated islets and in rat insulinoma-derived cells (RIN line), revealing a new tissue specificity of the L-PK gene. Our results suggest that this gene may be expressed in islet progenitor cells from which the different mature endocrine cells derive.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Polyomavirus Transforming / genetics
  • Base Sequence
  • Dietary Carbohydrates / adverse effects*
  • Gene Expression Regulation, Neoplastic
  • Genes, myc / genetics
  • Liver Neoplasms, Experimental / etiology*
  • Mice
  • Mice, Transgenic
  • Molecular Sequence Data
  • Organ Specificity
  • Pancreatic Neoplasms / etiology*
  • Promoter Regions, Genetic
  • Pyruvate Kinase / genetics*


  • Antigens, Polyomavirus Transforming
  • Dietary Carbohydrates
  • Pyruvate Kinase