BACKGROUND The human IGF2-P4 and IGF2-P3 promoters are highly active in a variety of human cancers, while existing at a nearly undetectable level in the surrounding normal tissue. Thus, a double promoter DTA-expressing vector was created, carrying on a single construct two separate genes expressing the diphtheria toxin a-fragment (DTA), from two different regulatory sequences, selected from the...

We hypothesize that loss of imprinting (LOI) of the insulin-like growth factor II (IGF2) gene is associated with a predisposition to sporadic colorectal cancer. We confirmed a previously known strong correlation between LOI and microsatellite instability and showed that LOI was not a consequence of microsatellite instability or mismatch repair deficiency. LOI of IGF2 correlated strongly with bi...

The H19-IGF2 locus within the imprinted cluster of the human chromosome 11, has been implicated in a variety of disorders and cancer pre-disposition including bladder cancer. BBN induced bladder cancer model in rats has identified both H19 and IGF2 among differentially expressed genes that are induced in response to carcinogen exposure. In this chapter, the role of both H19 and IGF2 genes in ca...

BACKGROUND The imprinted genes insulin-like growth factor 2 (IGF2) and H19 play important roles in various malignancies including hepatocellular carcinoma (HCC). MATERIALS AND METHODS We used DNA microarray and patient follow-up data to examine the relationship between expression of IGF2 and H19 and HCC. RESULTS We found that imbalances in levels of IGF2 and H19 transcripts were correlated ...

of the germ lines. Previous data have suggested that in nonmalignant tissues an imprint is constant throughout life and is not susceptible to modification, except during gametogenesis. The present study examines allelic expression of the IGF2 gene in human liver during postnatal development. The data show that the IGF2 gene is imprinted (i.e., monoallelically expressed) in liver at the age of 6...

Igf2 and H19 exhibit parent-of-origin-specific monoallelic expression. H19 is expressed from the maternal chromosome and Igf2 from the paternal. The two genes share enhancer elements and monoallelic expression of both genes is dependent on cis-acting sequences upstream of the H19 promoter. In this work we examine the mechanisms by which this region silences the maternal Igf2 allele and we demon...

Cloning by nuclear transfer is often associated with poor results due to abnormal nuclear reprogramming of somatic donor cells and altered gene expression patterns. We investigated the expression patterns of imprinted genes IGF2 and IGF2R in 33- to 36-day bovine embryos and chorio-allantoic membranes derived from in vivo- and in vitro-produced embryos by somatic cell nuclear transfer (SCNT), pa...

PURPOSE Frozen Shoulder Syndrome is a fibrosis of the shoulder joint capsule that is clinically associated with Dupuytren's disease, a fibrosis of the palmar fascia. Little is known about any commonalities in the pathophysiology of these connective tissue fibroses. β-catenin, a protein that transactivates gene expression, and levels of IGF2 mRNA, encoding insulin-like growth factor-II, are elev...

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. The imprinting of Igf2 is dependent upon an imprinting control region (ICR) that lies 90 kb 3' of the gene and acts as a chromatin insulator to block enhancers that lie further 3' on the c...