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

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.
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PMID:Immunohistochemical evaluation of epidermis overlying basal cell carcinomas. 768 54

The expression of transforming growth factor-alpha (TGF-alpha) in human differentiating leukemic cell lines and in circulating human eosinophils prompted the search for an analogous function in normal human bone marrow (BM) cells. Immunohistochemistry, using a monoclonal antibody directed to the mature form of the TGF-alpha molecule, showed TGF-alpha on the erythroblasts of normal donors. This novel property of erythroid cells was found on cells at all stages of maturation, most clearly on nucleated forms but to some extent also on erythrocytes within the BM. The presence of membrane-bound TGF-alpha on erythroblasts was confirmed by immunomagnetic cell sorting with polyclonal TGF-alpha antibodies; the recovered cells consisted almost entirely of erythroblasts. Using another monoclonal antibody directed to TGF-alpha, immunohistochemistry showed a different pattern of positive cells including eosinophilic precursor cells, in accordance with earlier findings in blood eosinophils. In addition, the TGF-alpha immunoreactivity was shown in promyelocytes and neutrophilic myelocytes. The presence of epidermal growth factor (EGF) receptor mRNA in BM cells was demonstrated by reverse transcription polymerase chain reaction, whereas EGF receptor-carrying cells were recognized by immunohistochemistry, using polyclonal antibodies directed to the cytoplasmic part of the EGF receptor. The EGF receptor-positive cell constituted about 3% of the nucleated BM cell population. It was classified as a blastlike cell of myelomonocytic origin by morphologic criteria and CD68 positivity. Our results may indicate a novel function of TGF-alpha in erythrocytic differentiation.
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PMID:Transforming growth factor-alpha (TGF-alpha) in human bone marrow: demonstration of TGF-alpha in erythroblasts and eosinophilic precursor cells and of epidermal growth factor receptors in blastlike cells of myelomonocytic origin. 772 72

Primary and metastatic ovarian cystadenocarcinomas, carcinomas of low malignant potential (borderline tumors), benign ovarian cystadenomas, and normal ovaries were compared for immunoperoxidase detection of the ligands epidermal growth factor (EGF), transforming growth factor-alpha (TGF-alpha), amphiregulin (AR), cripto, and the receptors, epidermal growth factor receptor (EGF-R), and c-erbB-2. This matrix analysis of these EGF family members indicated no specific pattern of ligand or receptor expression with a specific ovarian histologic category except in the case of AR and TGF-alpha. AR was detected almost exclusively in borderline tumors, suggesting that these tumors may not arise as a pathological continuum between benign cystadenomas and invasive cystadenocarcinomas. Second, the presence of TGF-alpha immunoreactivity in the absence of coexpression of cripto or EGF appeared to be associated only with adenocarcinomas of high grade and stage.
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PMID:Frequent immunohistochemical detection of EGF supergene family members in ovarian carcinogenesis. 781 96

Among the tissue, cellular, and molecular changes which take place during the development of squamous cell carcinoma (SCC) of the upper aerodigestive tract, only a limited number can be used as surrogate endpoint biomarkers (SEBs) in cancer chemoprevention trials. Molecular SEBs will be genes or gene products which can be measured accurately and reliably, are altered in intraepithelial neoplasia (dysplasia), correlate strongly with the true outcome (invasive cancer), and are modulated by a chemoprevention agent(s). To identify and modulate molecular SEBs in intraepithelial neoplasia of the upper aerodigestive tract, we studied expression of the epidermal growth factor receptor (EGFR), transforming growth factor-alpha (TGF-alpha), and HER-2/neu genes in oral leukoplakia before, during, and after treatment with 13-cis-retinoic acid, a vitamin A derivative. Four of nine patients treated for 3 months with 1 mg/kg/day of 13-cis-retinoic acid had complete resolution of their leukoplakia. Biopsies were taken of leukoplakia and adjacent normal-appearing mucosa before, during, and after treatment. Immunohistochemistry was performed using the BioGenex Super Sensitive Biotin-Streptavidin horseradish peroxidase detection system. Pretreatment expression of EGFR, TGF-alpha, and HER-2/neu in leukoplakia was increased when compared to normal-appearing mucosa. TGF-alpha expression decreased during treatment in leukoplakia, but not in normal-appearing mucosa, suggesting that TGF-alpha may serve as an intermediate endpoint in cancer chemoprevention trials.
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PMID:Retinoid modulation of biomarkers in oral leukoplakia/dysplasia. 782

Microsome factions prepared from the mammary glands of non-pregnant, pregnant and lactating sheep have been used to study binding of 125I-labelled transforming growth factor-alpha (TGF-alpha). Binding was dependent on microsomal protein concentration, time and temperature. It showed the characteristics of an epidermal growth factor (EGF) receptor, being displaced by TGF-alpha and EGF, but not by insulin or IGF-I. The non-linear curve fitting program LIGAND was used to determine affinity and number of binding sites. A single class of high-affinity binding sites was found. The apparent dissociation constant (Kd) was similar in all physiological states (2.43 +/- 0.27 mol/l x 10(-10), n = 23). Numbers of binding sites were lower in late-pregnant (20 weeks) and lactating sheep (14.07 +/- 2.45 fmol/mg protein, n = 10) than in non-pregnant, 10- or 15-week pregnant sheep (43.04 +/- 5.93 fmol/mg protein, n = 13). DNA synthesis by mammary alveolar epithelial cells cultured on collagen gels was increased twofold by TGF-alpha (maximum response at 10 micrograms/l; 1.8 nmol/l) but not by EGF. Cells derived from 15- to 20-week pregnant sheep responded significantly to TGF-alpha on day 3 of culture, but the response was delayed to day 4-5 of culture in cells from other physiological states. Dose-response was not significantly affected. TGF-alpha and IGF-I produced an additive effect on DNA synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Transforming growth factor-alpha: receptor binding and action on DNA synthesis in the sheep mammary gland. 789 Oct 19

The c-erbB-2 (HER-2/neu) protooncogene encodes an M(r) 185,000 transmembrane glycoprotein with intrinsic tyrosine kinase activity. Agonistic antibodies against p185c-erbB-2 enhance the cytotoxic effect of the DNA alkylator, cisplatin, against c-erbB-2-overexpressing human carcinoma cells (Hancock et al., Cancer Res., 51:4575-4580, 1991). We have studied the possible association between receptor signal transduction and cisplatin-mediated cytotoxicity utilizing the SKBR-3 human breast cancer cell line and the anti-p185 TAb 250 IgG1. TAb 250 induced tyrosine phosphorylation of p185 and the receptor substrate phospholipase C-gamma 1, as well as rapid association of these molecules in vivo. Simultaneously with phosphorylation, phospholipase C-gamma 1 catalytic activity measured in a [3H]phosphatidylinositol-4,5-bisphosphate hydrolysis assay was increased 61 +/- 12% above control. Preincubation of SKBR-3 cells with the tyrosine kinase inhibitor tyrphostin 50864-2 abrogated the enhancement of drug-mediated cell kill induced by TAb 250. The supraadditive drug/antibody effect was not seen in SKBR-3 cells with TAb 263, an anti-p185 IgG1 that does not induce receptor signaling or with TAb 250 in MDA-468 breast cancer cells which do not overexpress c-erbB-2. In addition, transforming growth factor-alpha increased cisplatin-induced cytotoxicity against NIH 3T3 cells overexpressing an epidermal growth factor receptor/c-erbB-2 chimera. Cellular uptake or efflux of [195mPt]cisplatin by SKBR-3 cells was not altered by TAb 250. Finally, simultaneous treatment of SKBR-3 cells with TAb 250 and cisplatin increased cisplatin/DNA intrastrand adduct formation and delayed the rate of adduct decay. Taken together these data support a direct association between p185c-erbB-2 signal transduction and inhibition of cisplatin-induced DNA repair.
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PMID:p185c-erbB-2 signal enhances cisplatin-induced cytotoxicity in human breast carcinoma cells: association between an oncogenic receptor tyrosine kinase and drug-induced DNA repair. 791 7

The expression of transforming growth factor-alpha (TGF-alpha), epidermal growth factor receptor (EGF-R) and oncogenes c-erbB-2, c-H-ras, c-myc, as well as estrogen (ER) and progesterone (PR) receptors were studied immunohistochemically in the tissue of 21 benign and 58 malignant human breast lesions. Twenty nine (50%) of 58 carcinomas were positive for EGF-R and c-erbB-2 product, 55 (94.8%) for c-myc product, 9 (15.5%) for c-H-ras product and 17 (29%) for TGF-alpha. Eighteen of 58 (31%) carcinomas were estrogen receptor positive and 22 (38%) were positive for progesterone receptor. No correlation was found between expression of each investigated parameter and the clinical stage or degree of histological differentiation of the carcinomas. However, a significant positive correlation was observed between lymph node involvement and c-erbB-2 and EGF-R/c-erbB-2 positive tumors. A strong correlation was also observed between high levels of EGF-R and low levels of estrogen receptor. In 15 of 17 cases we found simultaneous expression of EGF-R and TGF-alpha. We also found interesting patterns in concomitant expression of the investigated parameters suggesting a possible cascade of events that occur in breast cancer cells.
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PMID:Immunohistochemical detection of TGF-alpha, EGF-R, c-erbB-2, c-H-ras, c-myc, estrogen and progesterone in benign and malignant human breast lesions: a concomitant expression. 791 21

The expression of mRNA for epidermal growth factor (EGF), transforming growth factor-alpha (TGF-alpha), EGF receptor (EGFR) and c-erbB-2 genes and the immunoreactivity to these gene products were examined in 3 newly established human pancreatic carcinoma cell lines and their corresponding in vivo tumor lines using the Northern blot technique and the immunohistochemical method. All 3 cell lines expressed TGF-alpha, EGFR and 2 of the 3 lines expressed EGF and c-erbB-2 mRNAs. The immunohistochemical study showed immunoreactivity to EGF, TGF-alpha and EGFR in all these 3 cell lines and their corresponding in vivo tumor lines. These results indicate that the autocrine loop of EGF and/or TGF-alpha/EGFR in pancreatic carcinoma cells may be one of the important reasons for the uncontrolled growth of the pancreatic carcinoma. The c-erbB-2 overexpression in some of the cell lines may also contribute to the carcinogenesis or progression of this cancer.
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PMID:Expression of EGF, TGF-alpha, EGFR and c-erbB2 genes and their gene products in human pancreatic carcinoma cell lines. 794 34

The epidermal growth factor (EGF) receptor is an important mediator of intestinal epithelial cell proliferation. We studied cell-surface localization of this molecule in Caco-2 cells and characterized cellular responses to apical or basolateral EGF stimulation. 125I-labeled EGF bound almost exclusively to a 180-kDa molecule, existing as a single high-affinity population by Scatchard analysis. On basolateral membranes 13- to 15-fold more ligand binding was seen. Apical/basolateral differences were not significantly altered by incubation with either blocking antibody to EGF receptor or transforming growth factor-alpha (TGF-alpha) neutralizing antibody. Even though apical EGF receptors were demonstrated, only basolateral membrane stimulation with EGF increased tyrosine kinase activity and enhanced uptake of [3H]thymidine. Continuous exposure to EGF during culture significantly increased monolayer DNA content. These data demonstrate that Caco-2 cell proliferation is driven solely by basolateral membrane EGF receptor, despite the presence of lesser amounts of this molecule on the apical surface. Differences between apical and basolateral membrane receptor expression are not the result of polarized secretion of TGF-alpha or other EGF receptor ligands.
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PMID:Regulation of Caco-2 cell proliferation by basolateral membrane epidermal growth factor receptors. 797 52

The mRNA expression of transforming growth factor-alpha (TGF-alpha), epidermal growth factor receptor (EGFR), c-erbB-2 and c-met proto-oncogenes in eight newly established cell lines and 29 primary tumors of human non-small-cell lung carcinoma (NSCLC) have been investigated. In vitro, the expressions of TGF-alpha, c-erbB-2, and c-met were consistently high in adenocarcinomas, while EGFR was expressed highest in a squamous cell carcinoma cell line. There was linear correlation between the levels of expression of TGF-alpha and EGFR or c-erbB-2, and between EGFR and c-erbB-2. The c-met expression was also correlated with those of TGF-alpha, EGFR, and c-erbB-2. In vivo, The mean mRNA levels of TGF-alpha, EGFR, and c-met, but not c-erbB-2, were higher in carcinomas than in normal lung tissues (2.8, 1.7, and 3.0 times, respectively); however, only adenocarcinomas expressed a significantly higher level of c-erbB-2 than their corresponding normal tissues (2.2 times). In 20 patients whose paired normal and tumor tissue were examined, the percentage of cases with greater than twofold increase in expression in carcinomas than normal were 55% for both TGF-alpha and EGFR, 30% for c-erbB-2, and 47% for c-met. Among the histological subtypes of NSCLC, a higher percentage of adenocarcinomas than squamous cell carcinomas over-expressed these genes, especially c-erbB-2 and c-met. Over-expression is rarely the result of gene amplification. The results suggest a differential expression of growth factor and receptor genes among the various histological subtypes of NSCLCs.
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PMID:In vitro and in vivo expressions of transforming growth factor-alpha and tyrosine kinase receptors in human non-small-cell lung carcinomas. 809 69


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