Disease relevance of PEG10

• The product of the imprinted gene paternally expressed gene-10 (PEG10) has been reported to support proliferation in hepatocellular carcinomas, but how this gene is regulated has been an open question [1].
• As in the mouse model, we found positive, but not absolute, correlations between PEG10 and c-MYC in tissue arrays containing 161 human breast cancers (P < 0.002) and 30 prostate cancers (P = 0.014) [1].
• Understanding the molecular basis of the abnormal imprinting of PEG10 will shed new light on the process that leads to liver disease [2].
• In a mouse mammary tumor virus (MMTV)-MYC transgenic mouse model of breast cancer, most but not all of the mammary carcinomas had strongly increased Peg10 mRNA compared with normal mammary gland [1].
• In order to develop in vitro and animal models, the authors isolated an additional cell line (HB1) from a human hepatoblastoma and here report its characteristics in culture [3].

High impact information on PEG10

• Several genes including Glypican 3, spondin-2, PEG10, EDIL3 and Osteopontin are over-expressed in HCC vs. adjacent tissue whereas Ficolin 3 is the most consistently under-expressed gene [4].
• We find that MYC knockdown by RNA interference suppresses PEG10 expression in Panc1 pancreatic carcinoma and HepG2 hepatocellular carcinoma cells and that knockdown of PEG10 inhibits the proliferation of Panc1, HepG2, and Hep3B cells [1].
• Conversely, PEG10 was up-regulated by inducing c-MYC expression in a B-lymphocyte cell line [1].
• By immunohistochemistry, normal human breast and prostate epithelium was negative for the major isoform [reading frame-1 (RF1)] of PEG10 protein, but this cytoplasmic protein was strongly expressed in a subset of breast carcinomas in situ and invasive ductal carcinomas ( approximately 30%) and in a similar percentage of prostate cancers [1].
• Immunostaining of human placenta showed PEG10 and c-MYC proteins coexpressed in proliferating cytotrophoblast and coordinately lost in postmitotic syncytiotrophoblast [1].

Biological context of PEG10

• A retrotransposon-derived gene, PEG10, is a novel imprinted gene located on human chromosome 7q21 [5].
• These data suggest that PEG10 is derived from a retrotransposon that was previously integrated into the mammalian genome [5].
• Here we have analyzed the temporal regulation of mRNA expression of these genes in placenta and demonstrate that Syncytin gene activation is highest in term placenta, PEG10, downregulated at early hypoxic phase, and highly activated at 11-12 wk of gestation [6].
• Exogenous expression of PEG10 conferred oncogenic activity and transfection of hepatoma cells with antisense S-oligonucleotides suppressing PEG10 resulted in their growth inhibition [7].
• These findings link cancer genetics and epigenetics by showing that a classic proto-oncogene, MYC, acts directly upstream of a proliferation-positive imprinted gene, PEG10 [1].

Anatomical context of PEG10

• Through a genome-wide cDNA microarray, we identified that the paternally expressed gene 10 (PEG10) was highly expressed in a great majority of hepatocellular carcinomas, although its expression was absent in normal liver cells [7].
• Reverse transcription-PCR and Northern blot analysis showed a broad range of PEG10 expression in different tissues and cell types, i.e. human placenta, brain, kidney, endothelial cells, lymphoblasts, and HepG2 and HEK293 cells [8].
• PEG10 is distributed in the cytosol and associates with the nuclear membrane [2].
• Normal or subnormal facial nerve function (HB 1 or HB 2) was achieved in 7/9 cases (78%) evaluated at > or = 1 year after surgery [9].

Associations of PEG10 with chemical compounds

• Immunoblotting study demonstrated that SIAH1 also reduces the amount of PEG10 protein, which is known to be frequently overexpressed in HCC and to promote cell proliferation [10].
• A significant improvement has been achieved using two affinity chromatographic procedures, one exploiting the glycoprotein nature of the proteins and the other exploiting their ligand properties, which in combination resulted in considerable enrichment of HB1 and HB2 [11].
• Final report on the safety assessment of PEG-25 propylene glycol stearate, PEG-75 propylene glycol stearate, PEG-120 propylene glycol stearate, PEG-10 propylene glycol, PEG-8 propylene glycol cocoate, and PEG-55 propylene glycol oleate [12].

Physical interactions of PEG10

• Chromatin immunoprecipitation from Panc1 cells showed c-MYC bound to an E-box-containing region in the PEG10 first intron and site-directed mutagenesis showed that the most proximal E-box is essential for promoter activity [1].
• Using the two-hybrid system, we identified an ALK1-binding protein encoded by an ancient retroviral/retrotransposon element integrated as a single copy gene known as PEG10 on human chromosome 7q21 [8].

Other interactions of PEG10

• PEG10 is located near the SGCE (Sarcoglycan epsilon) gene, whose mouse homologue was recently shown to be imprinted [5].
• Involvement of PEG10 in human hepatocellular carcinogenesis through interaction with SIAH1 [7].
• Overexpression of a novel imprinted gene, PEG10, in human hepatocellular carcinoma and in regenerating mouse livers [2].

References