title: Diet-dependent carcinogenesis of pancreatic islets and liver in transgenic mice expressing oncogenes under the control of the L-type pyruvate kinase gene promoter.
abstract: 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.
authors.affiliation: Institut Cochin de Génétique Moléculaire, Génétique et Pathologie Moléculaires, INSERM U129, Paris, France.
authors.forename: N
authors.initials: N
authors.lastname: Cartier
authors.forename: L
authors.initials: L
authors.lastname: Miquerol
authors.forename: M
authors.initials: M
authors.lastname: Tulliez
authors.forename: N
authors.initials: N
authors.lastname: Lepetit
authors.forename: F
authors.initials: F
authors.lastname: Levrat
authors.forename: G
authors.initials: G
authors.lastname: Grimber
authors.forename: P
authors.initials: P
authors.lastname: Briand
authors.forename: A
authors.initials: A
authors.lastname: Kahn
mesh_terms: D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics; D001483:Base Sequence; D004040:Dietary Carbohydrates / Q000009:adverse effects*; D015972:Gene Expression Regulation, Neoplastic; D016259:Genes, myc / Q000235:genetics; D008114:Liver Neoplasms, Experimental / Q000209:etiology*; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009928:Organ Specificity; D010190:Pancreatic Neoplasms / Q000209:etiology*; D011401:Promoter Regions, Genetic; D011770:Pyruvate Kinase / Q000235:genetics*
chemical_list: D000952:Antigens, Polyomavirus Transforming; D004040:Dietary Carbohydrates; D011770:Pyruvate Kinase