Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04626 (erbB-2)
 5,251 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The pathogenesis of cutaneous paraneoplastic syndromes is still under discussion. Since many of these syndromes, including acanthosis nigricans, are proliferative skin disorders it is believed that products secreted by the tumour stimulate the keratinocytes to proliferate. Growth factors like transforming growth factor alpha (TGF-alpha) are known to be highly mitogenic for keratinocytes in vitro. Here we report on a patient with a poorly differentiated gastric cancer and a full clinical picture of acanthosis nigricans characterized by diffuse hyperkeratosis and multiple papillomatous lesions of the skin with involvement of the conjunctivae. In Southern blot analysis of the tumour tissue from this patient amplification of the epidermal growth factor (EGF) receptor, the common ligand for TGF-alpha and EGF, was shown. Immunohistochemically, prominent staining was found throughout the tumour using anti-TGF-alpha antibodies. In a series of 25 investigated gastric tumour biopsies, four tumours showed amplification of the EGF receptor and one additional biopsy was positive for TGF-alpha. Since there is no other report describing the link between TGF-alpha and acanthosis nigricans, except that of Ellis et al. 1987, we present a new case suggesting a possible link between growth factors and acanthosis nigricans maligna.
Arch Dermatol Res 1992
PMID:Further evidence that acanthosis nigricans maligna is linked to enhanced secretion by the tumour of transforming growth factor alpha. 144 75

The epidermal growth factor (EGF) receptor pathway is an important mediator of keratinocyte growth in vitro and both receptor and ligand components of this pathway are abnormally expressed in hyperproliferative epidermis. The purpose of this study was to examine interactions between the EGF receptor pathway and the insulin-like growth factor I/somatomedin C (IGF-I) receptor pathway in modulating the growth of cultured normal human keratinocytes. Short-term growth of keratinocytes in a chemically defined medium demonstrated that neither EGF nor IGF-I alone could support significant keratinocyte spreading or proliferation, but that a combination of EGF with IGF-I or high-dose insulin could. IGF-I or high-dose insulin transmodulates keratinocyte EGF receptor expression via the IGF-I receptor in a dose- and time-dependent manner, increasing EGF receptor binding an average of 1.8 times up to a maximum of fourfold without altering EGF binding affinity. Staining of normal human epidermis with an IGF-I receptor specific monoclonal antibody demonstrates that IGF-I receptors localize to the basal proliferative cell compartment, suggesting that IGF-I receptor and EGF receptor pathway interactions may play a role in the regulation of epidermal growth and in the pathogenesis of hyperproliferative skin diseases.
J Invest Dermatol 1991 Apr
PMID:Synergistic effects of epidermal growth factor (EGF) and insulin-like growth factor I/somatomedin C (IGF-I) on keratinocyte proliferation may be mediated by IGF-I transmodulation of the EGF receptor. 184 76

The localization of DNA replicating cells, epidermal growth factor (EGF) receptor-expressing cells and ras oncogene product p21 (p-21ras) positive cells were examined in various skin tumours to elucidate the role of EGF receptor and p21ras in the epidermis. Normal skin, keratoacanthoma (KA), solar keratosis (SK), Bowen's disease (BD), squamous cell carcinoma (SCC), basal cell carcinoma (BCC) and extramammary Paget's disease (PD) were studied. EGF receptors were seen in proliferating layers, where DNA replicating cells localize, but p21ras was found in the more differentiated layers. We conclude that EGF receptor expression is closely associated with cellular proliferation, but p21ras may play a role in the differentiation of cells in various skin tumours.
Br J Dermatol 1990 Jul
PMID:Association of EGF receptor expression with proliferating cells and of ras p21 expression with differentiating cells in various skin tumours. 220 27

Poly(A)+mRNAs were purified from the skin sheets of five psoriatic patients and three healthy individuals, and mRNA expression of epidermal growth factor (EGF) receptor gene was studied by Northern-blot technique using a cDNA probe of the whole EGF-receptor gene. Both psoriatic and normal skin had 5.3-kb and 11.0-kb mRNAs of the EGF-receptor gene. There existed no clear differences in the mRNA levels between psoriasis and normal controls. Since Nanney et al. has reported an increased number of EGF-receptors in active lesions of psoriasis, it has been speculated that the production of EGF-receptors is not increased, but rather that the down-regulation may be decreased, in psoriatic skin, resulting in the increased number of EGF-receptors.
J Dermatol 1990 Feb
PMID:Epidermal growth factor receptor mRNA is not increased in psoriatic skin. 232 20

Two methods have been used to examine epidermal growth factor (EGF) receptor distribution in human scalp and foreskin. The first employed [125I]EGF viable explants and autoradiography to determine the EGF binding pattern while the second used a monoclonal antibody to the human EGF receptor to map the distribution on frozen skin sections of an extracellular epitope on the EGF receptor. The [125I]EGF binding experiments showed accessible, unoccupied EGF receptors to be present on the epidermal basal cells (with reduced binding to spinous cells), the basal cells of the hair shaft and sebaceous gland, the eccrine sweat glands, capillary system, and the hair follicle outer root sheath, generally similar in pattern to that previously reported for full-thickness rat skin and human epidermis. The same areas also bound EGF-R1 but in addition the monoclonal antibody recognized a cone of melanin containing presumptive cortex cells, excluding the medulla, lying around and above the upper dermal papilla of anagen hair follicles, epithelial cells around the lower dermal papilla region, and in some tissue samples the cell margins of the viable differentiating layers of the epidermis. In a control study, to clarify whether EGF-R1 could recognize molecules unrelated to the EGF receptor, the EGF binding and EGF-R1 recognition profiles were compared on cultures of SVK14 cells, a SV40 transformed human keratinocyte cell line. EGF binding and EGF-R1 monoclonal antibody distribution on these cells was found to be similar, indicating that, at least for SVK14 cells, EGF-R1 binding provides a reliable marker for EGF binding. Explanations for the discrepancies between these two methods for determining EGF receptor distribution in human skin are discussed, including the possibility that latent EGF receptors, unable to bind [125I]EGF, may be present in some differentiating epithelial compartments.
J Invest Dermatol 1985 Sep
PMID:Differences in human skin between the epidermal growth factor receptor distribution detected by EGF binding and monoclonal antibody recognition. 241 22

The neu (c-erbB-2) gene encodes a transmembrane protein with tyrosine kinase activity that appears to be a growth factor receptor. Antibody was generated by immunization of rabbits with a synthetic polypeptide that was based on an internal sequence at the carboxy terminus of the molecule. This antibody was used to survey the expression of neu in human skin by immunohistochemistry. Significant protein was found in the squamous cell layer of the surface epidermis, in squamous cell carcinomas, in the external root sheath of hair follicles, and in eccrine gland secretory cells; it was poorly expressed in the basal cell layer and in a basal cell carcinomas. Increased neu expression appears to be associated with the differentiation of keratinocytes.
J Invest Dermatol 1989 Jun
PMID:Distribution of neu (c-erbB-2) protein in human skin. 247 Aug 27

The distribution of several markers of keratinocyte differentiation was studied in normal epidermis, basal cell carcinomas (BCCs), and squamous cell carcinomas (SCCs) using the immunoperoxidase technique on frozen sections of punch biopsy specimens. As markers a panel of chain-specific monoclonal antibodies (MoAbs) directed against cytokeratin (CK) 4, 8, 10, 13, 18 and 19, a polyclonal antiserum against involucrin, as well as a MoAb against the epidermal growth factor (EGF) receptor were used. In 15 out of 19 BCCs tested, expression of CK 8 was seen. Only a few individual cells in a limited number of BCCs showed positive staining for CK 4, 18, or 19. No expression of CK 10 was seen except for some foci of cell keratinization. Involucrin was not found in BCCs except for some squamous horn cysts. In all BCC cells expression of EGF receptor was found. In the suprabasal layers of normal epidermis from SCC patients, positive staining for CK 10 was seen. A few individual cells in a limited number of SCCs showed positive staining for CK 4, 8, or 18. Involucrin was expressed in the center of SCCs and in the upper layers of normal epidermis. Expression of EGF receptor was found in all SCC cells. These results demonstrate differences in cellular origin and differentiation between BCC and SCC.
Arch Dermatol Res 1989
PMID:Expression of EGF receptor, involucrin, and cytokeratins in basal cell carcinomas and squamous cell carcinomas of the skin. 247 80

In a previous study on neonatal rat skin (Green MR, Basketter DA, Couchman JR, Rees DA: Dev Biol 100:506-512, 1983) a close positive correlation was found between epidermal growth factor (EGF) receptor tissue distribution and areas of potential epithelial cell proliferation. We now report on the binding distribution of [125I]EGF, representing the tissue localization of available EGF receptors, during embryonic rat skin development including hair follicle formation and the adult hair growth cycle. At 16 days embryonic development a relatively low receptor density is seen over all the epidermal cell layers but by 17 days, with the onset of very rapid epidermal proliferation, labeling increases and becomes restricted to the basal epidermal cells. Between 17 and 20 days embryonic development, available receptors for EGF are consistently absent from epidermal basal cells overlaying the dermal condensates marking the first stage of hair follicle development. This restricted and temporary loss of EGF receptors above these specialized mesenchymal condensates implies a role for the EGF receptor and possibly EGF or an EGF-like ligand in stimulating the epithelial downgrowth required for hair follicle development. In the anagen hair bulb, receptors for EGF are detected over the outer root sheath and the epithelial cell layers at the base of the follicle and show a correlation with the areas of epithelial proliferation in the hair bulb. During the catagen and telogen phases of the hair cycle, receptors are observed in high numbers on all the undifferentiated or dedifferentiating cells of the degenerating epithelial strand and secondary hair germ. Dermal cells are, in general, less heavily labeled than the basal epithelial cells of skin except for the developing striated muscle (panniculus carnosus) in embryonic skin which is more heavily labeled. The data are discussed in terms of a possible role for the EGF receptor and associated EGF or EGF-like ligands in specific areas of epithelial tissue morphogenesis during embryonic skin maturation, hair follicle development, and hair cycling.
J Invest Dermatol 1984 Aug
PMID:Distribution of epidermal growth factor receptors in rat tissues during embryonic skin development, hair formation, and the adult hair growth cycle. 608 42

The membranes from epidermoid carcinoma cells (A-431) that were surface iodinated while intact using catalysis by lactoperoxidase and 125I as iodide contain one major labeled protein of Mr = 180,000. This protein is clearly iodinated on the outside of the intact cell because it is not the major protein labeled when isolated membranes are iodinated. This major surface-iodinated protein is almost certainly the epidermal growth factor (EGF) receptor, since both have the same Mr and have identical sensitivity to proteases. Both are nearly quantitatively converted from an Mr = 180,000 form to an Mr = 160,000 form by an endogenous calcium-activated neutral protease when cells are broken in the presence of calcium. Both are degraded by trypsin only if trypsin has access to the inside of the cell. This latter finding implies that the surface-iodinated EGF receptor spans the plasma membrane. Since the EGF receptor is an autophosphorylating kinase whose activity is enhanced in the presence of EGF, the receptor was labeled and identified using [gamma-32P] ATP. While both iodination and EGF-enhanced phosphorylation occur on tyrosine residues, peptide mapping of the iodinated or phosphorylated Mr = 180,000 band showed that different peptides were being labeled. Since the EGF receptor-kinase spans the plasma membrane, the peptide iodinated on the surface of the intact cell must be different from the peptides that are probably autophosphorylated on the cytoplasmic side of the membrane.
J Invest Dermatol 1984 Apr
PMID:Surface iodination of epidermal growth factor receptors in intact cells. 632 89

We have examined the character and carcinogenic properties of the normal-appearing epidermis overlying basal cell carcinomas by immunohistochemical methods, employing a series of monoclonal antibodies. The labelling index was significantly increased in the atrophic epidermis overlying basal cell carcinomas (solid type, n = 20), compared with the epidermis overlying or adjacent to squamous cell carcinoma (n = 20), keratoacanthoma (n = 10), dermatofibroma (n = 10), neurofibroma (n = 10), soft fibroma (n = 10), pyogenic granuloma (n = 10) and cutaneous leiomyoma (n = 5). Cells which expressed epidermal growth factor (EGF) receptor were detected in all layers of the epidermis over the basal cell carcinomas, but not the other tumours. Basement membrane-related antigens, including bullous pemphigoid antigen and GB3 antigen, were decreased in the epidermis. AE1, the monoclonal antibody against basal cell keratin, reacted with the uppermost layers of the normal-appearing epidermis overlying the basal cell carcinomas. ICAM-1 expression was very weak in the overlying epidermis. The dermis subjacent to the proliferating epidermis showed staining for transforming growth factor-alpha (TGF-alpha), strong positive PECAM-1 staining of endothelium, and numerous HLA-DR-positive cells. From these results, we suggest that the proliferative activity in the epidermis overlying basal cell carcinomas is not a state induced by the dermal infiltrate, but represents carcinogenic activity of the epidermis.
Br J Dermatol 1993 Jun
PMID:Immunohistochemical evaluation of epidermis overlying basal cell carcinomas. 768 54


1 2 3 4 Next >>