Deregulation of both imprinted and expressed alleles of the insulin-like growth factor 2 gene during beta-cell tumorigenesis.
In a mouse model of multistage carcinogenesis elicited by the SV40 large T-antigen (Tag) oncogene in pancreatic beta cells, the gene for insulin-like growth factor IGF2 is focally up-regulated and functionally implicated in tumour development. The IGF2 gene is differentially regulated in normal tissues: the paternal allele is transiently expressed during embryogenesis, whereas the maternal allele is genomically imprinted and inactive. Crossbred mice carrying the Tag oncogene and a disruption of either the paternal or maternal allele of IGF2 reveal that both alleles are co-activated early during tumour development, and that each contributes to malignant hyperproliferation and consequent tumour volume.
Christofori
G
G
Department of Biochemistry & Biophysics, University of California, San Francisco 94143-0534, USA.
Naik
P
P
Hanahan
D
D
D000483:Alleles; D000818:Animals; D001483:Base Sequence; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D018392:Genomic Imprinting; D005838:Genotype; D007335:Insulin-Like Growth Factor II / Q000096:biosynthesis / Q000235:genetics*; D007515:Islets of Langerhans / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000096:biosynthesis / Q000235:genetics; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000473:pathology*; D010641:Phenotype; D062085:RNA, Long Noncoding; D012333:RNA, Messenger / Q000096:biosynthesis; D022661:RNA, Untranslated; D015854:Up-Regulation
C094335:H19 long non-coding RNA; D009124:Muscle Proteins; D062085:RNA, Long Noncoding; D012333:RNA, Messenger; D022661:RNA, Untranslated; D007335:Insulin-Like Growth Factor II