Immunolocalization of Epidermal Growth Factor Receptors in Normal Developing Human Skin

Nanney, Lillian B.; Stoscheck, Christa M.; King, Lloyd E.; Underwood, Robert; Holbrook, Karen A.

doi:10.1111/1523-1747.ep12874601

Cited by 181 publications

(109 citation statements)

References 36 publications

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“…9 Demonstration of EGFR expression in the human fetus has, until now, been limited to a narrower range of tissues but has been described in placenta, 10 ovary and uterus, 11 lung, 12 keratinocyte, endothelial and skeletal muscle cells. 13 These results suggest that one or more ligand(s) for EGFR are widely involved in embryonic and fetal development. Other studies provide evidence for a specific role in growth.…”

Section: Introductionmentioning

confidence: 84%

Human EGFR, a candidate gene for the Silver-Russell syndrome, is biallelically expressed in a wide range of fetal tissues

et al. 1998

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Maternal uniparental disomy of chromosome 7 (mUPD7) has been reported in around 10% of cases of Silver-Russell syndrome (SRS). This suggests that at least one gene on chromosome 7 is imprinted and involved in the pathogenesis of this condition. One candidate is epidermal growth factor receptor (EGFR) which maps to chromosome 7p12, a region homologous to an imprinted region on mouse chromosome 11. Using a restriction fragment length polymorphism, biallelic expression of EGFR was found in a range of normal human fetal tissues. Expression was also demonstrated in fibroblasts and lymphoblasts from SRS patients with mUPD7. Thus no evidence that EGFR is imprinted was found, making its involvement in SRS unlikely. However, EGFR was shown to be widely expressed in the human fetus, evidence that this gene plays an important role in early development.

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Section: Introductionmentioning

confidence: 84%

Human EGFR, a candidate gene for the Silver-Russell syndrome, is biallelically expressed in a wide range of fetal tissues

et al. 1998

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“…Previous reports have shown that the epidermal growth factor receptor is downregulated in the basal cells of primary human follicle placodes (Nanney et al, 1990). However, the concomitant downregulation of FGFR2(IIIb) receptor specifically within the epithelial placodes of developing primary follicles is a novel observation that differs from previous reports (Danilenko et al, 1995).…”

Section: Egfr and Fgfr2(iiib) Are Coordinately Downregulated During Pmentioning

confidence: 74%

KGF and EGF signalling block hair follicle induction and promote interfollicular epidermal fate in developing mouse skin

et al. 2009

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A key initial event in hair follicle morphogenesis is the localised thickening of the skin epithelium to form a placode, partitioning future hair follicle epithelium from interfollicular epidermis. Although many developmental signalling pathways are implicated in follicle morphogenesis, the role of epidermal growth factor (EGF) and keratinocyte growth factor (KGF, also known as FGF7) receptors are not defined. EGF receptor (EGFR) ligands have previously been shown to inhibit developing hair follicles; however, the underlying mechanisms have not been characterised. Here we show that receptors for EGF and KGF undergo marked downregulation in hair follicle placodes from multiple body sites, whereas the expression of endogenous ligands persist throughout hair follicle initiation. Using embryonic skin organ culture, we show that when skin from the sites of primary pelage and whisker follicle development is exposed to increased levels of two ectopic EGFR ligands (HBEGF and amphiregulin) and the FGFR2(IIIb) receptor ligand KGF, follicle formation is inhibited in a time-and dose-dependent manner. We then used downstream molecular markers and microarray profiling to provide evidence that, in response to KGF and EGF signalling, epidermal differentiation is promoted at the expense of hair follicle fate. We propose that hair follicle initiation in placodes requires downregulation of the two pathways in question, both of which are crucial for the ongoing development of the interfollicular epidermis. We have also uncovered a previously unrecognised role for KGF signalling in the formation of hair follicles in the mouse.

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“…12 EGFR expression in the developing human fetus has been detected in a wide variety of tissues, 31 including skeletal muscle tissue. 32 The expression of EGFR has been also demonstrated in rhabdomyosarcoma cell lines, in which abrogation of EGFR expression was found to impair proliferative ability. 23 Likewise, ErbB-2 is required for myoblast cell survival, 33 and ectopic expression of ErbB-2 in a transgenic mouse that lacks the p53 tumor suppressor gene has been shown to promote rhabdomyosarcoma development 34 (although p53 mutation frequency has been found to be extremely low in rhabdomyosarcoma tumors 35 ).…”

Section: Discussionmentioning

confidence: 99%

Expression and genomic status of EGFR and ErbB-2 in alveolar and embryonal rhabdomyosarcoma

et al. 2006

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Both epidermal growth factor receptor (EGFR) and ErbB-2 play an important role in cancer biology and constitute promising molecular targets of therapy. EGFR and ErbB-2 expression has been observed in rhabdomyosarcoma cell lines but not analyzed systematically in rhabdomyosarcoma tumors. Tissue microarray sections representing 66 rhabdomyosarcoma tumors (34 embryonal rhabdomyosarcoma, 32 alveolar rhabdomyosarcoma) were surveyed by immunohistochemistry using antibodies specific for EGFR and ErbB-2. Immunostains were assessed for intensity (0: no immunostaining; 1: weak; 2: moderate; 3: strong) and percentage of at least 500 neoplastic cells exhibiting membranous or membranous and cytoplasmic immunostaining. EGFR and ErbB-2 expression was considered positive if the product of intensity and percentage was greater than 10. Patients had a median age of 5.7 years (range 8 months-19.1 years), and of 65/ 66 patients, 38 were males and 27 were females. Expression of ErbB-2 was identified in 22/66 (33%) cases and tended to be more frequent in the alveolar subtype (13/32, 41%, vs 9/34, 26%, P ¼ 0.30). Expression of EGFR was identified in 31/66 (47%) cases and correlated with the embryonal subtype (26/34, 76%, vs 5/32, 16%, Po0.0001) independent of stage, age, and gender. Coexpression of EGFR and ErbB-2 was identified in eight tumors, of which six were embryonal rhabdomyosarcoma. None of the cases exhibited EGFR or ErbB-2 gene amplification, as assessed using fluorescence in situ hybridization. Furthermore, analysis of 11 additional rhabdomyosarcoma tumors (six alveolar; five embryonal) revealed no evidence of mutations in EGFR exons 18, 19, 20, and 21. In summary, expression of EGFR and/or ErbB-2 is detected in a sizeable subset of rhabdomyosarcoma tumors without evidence of EGFR or ErbB-2 amplification or mutations in the EGFR tyrosine kinase domain. Notably, expression of EGFR correlates with the embryonal subtype, which is also more likely to coexpress EGFR and ErbB-2.

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Immunolocalization of Epidermal Growth Factor Receptors in Normal Developing Human Skin

Cited by 181 publications

References 36 publications

Human EGFR, a candidate gene for the Silver-Russell syndrome, is biallelically expressed in a wide range of fetal tissues

Human EGFR, a candidate gene for the Silver-Russell syndrome, is biallelically expressed in a wide range of fetal tissues

KGF and EGF signalling block hair follicle induction and promote interfollicular epidermal fate in developing mouse skin

Expression and genomic status of EGFR and ErbB-2 in alveolar and embryonal rhabdomyosarcoma

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