Disease relevance of Insulin-Like Growth Factor-2

• Disruption of insulin-like growth factor 2 imprinting in Beckwith-Wiedemann syndrome [1].
• We describe a 2.2-kbp microdeletion in the H19/insulin-like growth factor 2 (IGF2)-imprinting center eliminating three target sites of the chromatin insulator protein CTCF that we believe here is necessary, but not sufficient, to cause BWS and Wilms' tumor [2].
• Insulin-like growth factor 2 and potential regulators of hemangioma growth and involution identified by large-scale expression analysis [3].
• Many tumours, and some developmental disorders, exhibit loss of imprinting (LOI) in key genes such as insulin-like growth factor 2 (IGF2) which often results in hyperplasia and is associated with cancer [4].
• One of the most studied imprinted genes encodes insulin-like growth factor 2, and aberrant imprinting and DNA methylation of this gene is associated with the growth disorders Beckwith-Wiedemann and Silver-Russell syndromes and many human cancers [5].

Psychiatry related information on Insulin-Like Growth Factor-2

• OBJECTIVE: An interesting candidate gene for eating disorders is the gene for insulin-like growth factor 2 (IGF2) [6].

High impact information on Insulin-Like Growth Factor-2

• The paternally expressed gene insulin-like growth-factor 2 (Igf2) is separated by approximately 100 kb from the maternally expressed noncoding gene H19 on mouse distal chromosome 7 [7].
• Here we used a GAL4 knock-in approach as well as the chromosome conformation capture technique to show that the differentially methylated regions in the imprinted genes Igf2 and H19 interact in mice [7].
• These results suggest that increased in utero expression of paternal INS or IGF2 due to the class I INS VNTR allele may predispose offspring to postnatal fat deposition [8].
• Finally, we have genetically and physically mapped Mash2 to the distal region of chromosome 7, within a cluster of imprinted genes, including insulin-2, insulin-like growth factor-2 and H19 [9].
• To study insulin-like growth factor 2 (IGF2) imprinting in BWS (Beckwith-Wiedemann syndrome, an overgrowth syndrome associated with Wilms and other embryonal tumours), we examined allele-specific expression using an Apal polymorphism in the 3' untranslated region of IGF2 [1].

Chemical compound and disease context of Insulin-Like Growth Factor-2

• Gastric cancer: the role of insulin-like growth factor 2 (IGF 2) and its receptors (IGF 1R and M6-P/IGF 2R) [10].

Biological context of Insulin-Like Growth Factor-2

• Thus the parental imprinting of IGF2 appears to be evolutionarily conserved from mouse to man and has implications for the generation of the Beckwith-Wiedemann syndrome [11].
• Differentially methylated regions in Igf2 and H19 contain chromatin boundaries, silencers and activators and regulate the reciprocal expression of the two genes in a methylation-sensitive manner by allowing them exclusive access to a shared set of enhancers [7].
• We show here, by exploiting sequence polymorphisms in exon nine of the human insulin-like growth factor 2 (IGF2) gene, that only the paternally-inherited allele is active in embryonic and extra-embryonic cells from first trimester pregnancies [11].
• The somatic overgrowth of heterozygotes for the maternal deletion is attributed to a gain of function of insulin-like growth factor 2, rather than a loss of function of H19 [12].
• The identical expression during development of the 3'-most genes in the cluster, Igf2 and H19, led to the proposal that their imprinting was mechanistically linked through a common set of transcriptional regulatory elements [13].

Anatomical context of Insulin-Like Growth Factor-2

• These results establish that H19 and Igf2 utilize the same endoderm enhancers, but on different parental chromosomes [13].
• We show here, by in situ hybridization, that the insulin-like growth factor 2 (IGF-2) gene expression is particularly active in the cytotrophoblasts, which dominate these structures [14].
• By using in situ chromosomal hybridization and Southern blot analysis to examine RPMI 8402 cells, we determined that the break at 14q11 occurs within the variable region sequences of the T-cell receptor alpha-chain gene (TCRA); the break at 11p15 occurs between the HRAS1 gene and the genes for insulin and the insulin-like growth factor 2 [15].
• We have examined the allele-specific expression of IGF2 and H19 in fibroblasts derived from patients with sporadic Beckwith-Wiedemann syndrome (BWS), a fetal overgrowth syndrome associated with an imprinted locus on 11p15 [4].
• The insulin-like growth factor 2 gene (Igf2) is imprinted in most somatic tissues of the mouse with the exception of the choroid plexus and leptomeninges of the brain, where it is expressed from both alleles [16].

Associations of Insulin-Like Growth Factor-2 with other chemical compounds

• More importantly, the bisulfite genomic-sequencing allowed us to show that the methylation pattern of the paternal allele of the Igf2 gene is affected in trans by deletions of the active maternal allele of the H19 gene [17].
• Igf2r encodes a trans-membrane receptor that transports mannose-6-phosphate tagged proteins and insulin-like growth factor 2 to lysosomes [18].
• We show that p57(Kip2) (cyclin-dependent kinase inhibitor protein 2) and Igf2 (insulin-like growth factor 2) are induced by inhibiting histone deacetylases; however, their activated state is reversed quickly by withdrawal of trichostatin A [19].
• TNF-alpha-308G/A, IL6-174G/C, IGF2 820G/A, TGFB1-509C/T, and CYP11B2-344T/C genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) [20].
• DNA synthesis of MCF-7 cells stimulated by insulin-like growth factor 1, insulin-like growth factor 2, basic fibroblast growth factor or transforming growth factor alpha was inhibited by similar concentrations of kievitone (IC50 values 1-3 microM) [21].

Gene context of Insulin-Like Growth Factor-2

• Two of them, insulin-like growth factor-2 (Igf-2) and H19, map to the distal end of mouse chromosome 7, but are imprinted in opposite directions [22].
• The distal region of mouse chromosome 7 contains a cluster of imprinted genes that includes H19 and Igf2 (insulin-like growth factor 2) [23].
• Deregulation of one or more imprinted genes located at chromosome 11p15.5, of which insulin-like growth factor 2 (IGF2) is the most likely candidate, is believed to cause BWS, whereas the etiology of KTWS is completely obscure [24].
• The result indicates that Grb10 action is essentially independent of insulin-like growth factor 2, providing evidence that imprinting acts on at least two major fetal growth axes in a manner consistent with parent-offspring conflict theory [25].
• The M6P/IGF2R functions in the inactivation of the mitogen IGF2 and in the activation of the growth inhibitor, transforming growth factor beta [26].

Analytical, diagnostic and therapeutic context of Insulin-Like Growth Factor-2

• Using DNA microarrays representing approximately 10,000 human genes, we identified insulin-like growth factor 2 (IGF-2) as a potentially important regulator of hemangioma growth [3].
• We previously demonstrated an association between the insulin-like growth factor 2 (IGF2) gene 3'-untranslated region (3'-UTR) ApaI polymorphism and body mass index (BMI) in over 2500 middle-aged Caucasoid males [27].
• The expression of the insulin-like growth factor-2 (IGF-2) gene was studied by means of both in situ hybridization and immunohistochemistry in eight cases of Wilms' tumor with different histological features [28].
• Insulin-like growth factor-2 (IGF-2) was identified in these HPLC fractions, and the basophil-stimulating activity was inhibited by an anti-IGF-2-neutralizing Ab [29].
• Somatomedin (Sm) levels throughout pregnancy were determined in a longitudinal study of four normal women and three patients with GH deficiency by use of the RIA for Sm-A, a newly developed RIA for insulin-like growth factor 2 (IGF-2), and the placenta RRA for Sm-A [30].

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