Disease relevance of Ereg

• Additionally, in contrast to previous hypotheses, Ereg deficiency does not alter intestinal cancer susceptibility, as assayed in the ApcMin model, despite showing robust expression in developing tumors [1].
• Dermatitis due to epiregulin deficiency and a critical role of epiregulin in immune-related responses of keratinocyte and macrophage [2].
• Increase in amphiregulin and epiregulin in prostate cancer xenograft after androgen deprivation-impact of specific HER1 inhibition [3].
• Involvement of deregulated epiregulin expression in tumorigenesis in vivo through activated Ki-Ras signaling pathway in human colon cancer cells [4].

High impact information on Ereg

• Wound healing in the skin in EP(-/-) mice was not impaired in vivo, nor was the growth rate of keratinocytes from EP(-/-) mice different from that of WT mice in vitro [2].
• These findings, taken together, suggested that EP plays a critical role in immune/inflammatory-related responses of keratinocytes and macrophages at the barrier from the outside milieu and that the secreted and membrane-bound forms of EP have distinct functions [2].
• Epiregulin, an epidermal growth factor family member, acts as a local signal mediator and shows dual biological activity, stimulating the proliferation of fibroblasts, hepatocytes, smooth muscle cells, and keratinocytes while inhibiting the growth of several tumor-derived epithelial cell lines [1].
• However, Ereg null mice are highly susceptible to cancer-predisposing intestinal damage caused by oral administration of dextran sulfate sodium [1].
• Although epiregulin is broadly expressed and regulated both spatially and temporally, Ereg null mice show no overt developmental defects, reproductive abnormalities, or altered liver regeneration [1].

Biological context of Ereg

• The predicted amino acid sequence revealed that the purified epiregulin peptide of 46-amino acids was synthesized as an internal segment of a 162-amino acid putative transmembrane precursor [5].
• A cDNA clone encoding a novel epidermal growth factor (EGF)-related growth regulator, epiregulin, was isolated from a cDNA library prepared from a mouse fibroblast-derived tumor cell line, NIH3T3/clone T7 [5].
• Epiregulin stimulated cell proliferation to a significant extent [6].
• In this report, to further assess the role of epiregulin in innate immunity, we measured IL-6 production levels upon lipopolysaccharide and peptidoglycan stimulation in antigen presenting cells including macrophages and dendritic cells [7].
• Luciferase reporter assays using a vector harboring the first 125 base pairs of the epiregulin rat promoter revealed an increase in signal on TCDD treatment, which was lost upon mutation of the DRE [8].

Anatomical context of Ereg

• Epiregulin exhibited bifunctional regulatory properties: it inhibited the growth of several epithelial tumor cells and stimulated the growth of fibroblasts and various other types of cells [9].
• Epiregulin, a novel epidermal growth factor (EGF)-related growth regulating peptide, was purified from conditioned medium of the mouse fibroblast-derived tumor cell line NIH3T3/clone T7 [9].
• Epiregulin. A novel epidermal growth factor with mitogenic activity for rat primary hepatocytes [9].
• This investigation demonstrates that the expression of two additions to the family, betacellulin and epiregulin, are exquisitely restricted to the mouse uterine luminal epithelium and underlying stroma adjacent to the implanting blastocyst [10].
• These results provide evidence that expression of betacellulin and epiregulin in the uterus requires the presence of an active blastocyst and suggest an involvement of these growth factors in the process of implantation [10].

Associations of Ereg with chemical compounds

• Epiregulin stimulated tyrosine phosphorylation of a 170 kDa protein, which represents the EGF receptor, in a dose-dependent fashion [6].
• In acute experiments, epiregulin was able to potentiate insulin release in the presence of glucose or arginine, in the two cell lines [11].

Physical interactions of Ereg

• These findings suggest that epiregulin plays important roles in regulating the growth of epithelial cells and fibroblasts by binding to receptors for EGF-related ligands [9].

Regulatory relationships of Ereg

• The aryl hydrocarbon receptor directly regulates expression of the potent mitogen epiregulin [8].
• Treatment with epiregulin promoted greater epidermal proliferation and thickening than epidermal growth factor or vehicle due to an expansion of the proliferative compartment of keratinocytes [12].
• Epiregulin stimulates proliferation of rabbit gastric cells in primary culture through autophosphorylation of the epidermal growth factor receptor [6].
• Role of epiregulin in peptidoglycan-induced proinflammatory cytokine production by antigen presenting cells [7].

Other interactions of Ereg

• RESULTS: A fraction of growth factors showed a steady increase in the mRNA expression reaching between fourfold and eightfold 30 days after castration, including amphiregulin (P < 0.005) and epiregulin (P < 0.001) [3].
• These results demonstrate that AhR directly increases epiregulin expression, which could play an important role in TCDD mediated tumor promotion observed in rodent models [8].
• The promoter region of epiregulin has a dioxin responsive element (DRE) 56 nucleotides upstream of the transcription start site, along with three potential Sp1 binding sites [8].
• These results indicated that epiregulin may have a critical role in the regulation of peptidoglycan-mediated proinflammatory cytokine production in antigen presenting cells and innate immunity [7].
• The aim of this study was to determine whether epiregulin, a novel member of EGF-related growth factor family, was able to affect proliferation and secretory function of rat insulinoma INS-1E and RINm5F cell lines [11].

Analytical, diagnostic and therapeutic context of Ereg

• Gene targeting was used to insert a lacZ reporter into the mouse Ereg locus and to ablate its function [1].
• Although epiregulin transcript was not detected in several adult normal tissues by Northern blot analysis, approximately 4.8-kb transcript was present in 7-day-old mouse embryo and then diminished to very low or undetectable levels [5].
• Molecular cloning of mouse epiregulin, a novel epidermal growth factor-related protein, expressed in the early stage of development [5].
• Using real time quantitative PCR (qPCR), it was established that TCDD upregulates epiregulin gene expression [8].

References