Diet-dependent carcinogenesis of pancreatic islets and liver in transgenic mice expressing oncogenes under the control of the L-type pyruvate kinase gene promoter.
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.
Cartier
N
N
Institut Cochin de Génétique Moléculaire, Génétique et Pathologie Moléculaires, INSERM U129, Paris, France.
Miquerol
L
L
Tulliez
M
M
Lepetit
N
N
Levrat
F
F
Grimber
G
G
Briand
P
P
Kahn
A
A
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*
D000952:Antigens, Polyomavirus Transforming; D004040:Dietary Carbohydrates; D011770:Pyruvate Kinase