Medulloblastoma (MB) can arise in the cerebellum due to genetic activation of the Sonic Hedgehog (Shh) signaling pathway. During normal cerebellum development, Shh spurs the proliferation of granule neuron precursors (GNP), the precursor cells of MB. Mutations in the Shh receptor gene patched1 (ptc1+/-) lead to increased MB incidence in humans and mice. MB tumorigenesis in mice heterozygous for...

The Mendelian inheritance is based on the fundamental rule in which mammalian genes are expressed equally from two homologous biparental alleles. Recently a small number of genes have been identified to show an exception to this rule in that homologous alleles can function differently in somatic cells depending on whether they come from the mother or the father. This intriguing biological pheno...

The adjacent insulin-like growth factor 2 (IGF2) and H19 genes are imprinted in most normal human tissues, but imprinting is often lost in tumors. The mechanisms involved in maintenance of imprinting (MOI) and loss of imprinting (LOI) are unresolved. We show here that osteosarcoma (OS) tumors with IGF2/H19 MOI exhibit allele-specific differential methylation of a CTCF-binding site upstream of H...

Patients with adrenocortical carcinoma (ACC) need new treatment options. The aim of this study was to evaluate the effects of the mTOR inhibitors sirolimus and temsirolimus on human ACC cell growth and cortisol production. In H295, HAC15, and SW13 cells, we have evaluated mTOR, IGF2, and IGF1 receptor expressions; the effects of sirolimus and temsirolimus on cell growth; and the effects of siro...

Transcription factor zinc-finger BED domain-containing protein 6 (ZBED6) is unique to placental mammals and regulates insulin-like growth 2 (IGF2) expression, which lead muscle growth. However, the effect of ZBED6 on spleen still elusive. In this study, we explored regulation growth, results showed knockout (ZBED6 KO) pigs had heavier spleens than wild-type (WT) pigs. To analyze mechanism incre...

H19 and Igf2 are reciprocally imprinted genes that lie 90 kb apart on mouse chromosome 7. The two genes are coexpressed during development, with the H19 gene expressed exclusively from the maternal chromosome and Igf2 from the paternal chromosome. It has been proposed that their reciprocal imprinting is governed by a competition between the genes for a common set of enhancers. The competition o...

Paternally expressed Insulin-like Growth Factor II (IGF2) encodes a gene whose protein product functions as a potent growth mitogen. Overexpression of IGF2 has been implicated in a wide number of disorders and diseases. IGF2 is regulated in part by differential methylation of the two parentally derived alleles. The differentially methylated region (DMR) located upstream of the imprinted promote...

BACKGROUND The human IGF2-P4 and H19 promoters are highly active in a variety of human cancers, while existing at a nearly undetectable level in the surrounding normal tissue. Single promoter vectors expressing diphtheria toxin A-fragment (DTA) under the control regulation of IGF2-P4 or H19 regulatory sequences (IGF2-P4-DTA and H19-DTA) were previously successfully used in cell lines, animal mo...

Insulin-like growth factor antisense gene (Igf2as) expression was investigated in different mouse tissues during development, in differentiating C2C12 cells and in a ΔDMR1-U2 knockout mouse model. The expression levels of Igf2as were high in fetal and newborn liver and muscle tissues compared to adults. The Igf2as gene was also expressed in placenta and in brain. The expression data suggests th...

The amount of Insulin Growth Factor 2 (IGF2) controls the rate embryonal and postnatal growth. IGF2 adjacent H19 are imprinted genes telomeric cluster in 11p15 chromosomal region regulated by differentially methylated regions (DMRs) or imprinting centers (ICs): H19/IGF2:IG-DMR (IC1). Dysregulation due to IC1 Loss-of-Methylation (LoM) Gain-of-Methyaltion (GoM) causes Silver–Russell syndrome (SRS...