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)

The structure and expression of the proto-oncogene c-erbB-2 was studied in 86 patients with transitional cell carcinoma. Initial tissue samples comprised 37 grade 1, 32 grade 2 and 13 grade 3 tumours and four cases of carcinoma in situ. At the time of this first tumour sample, amplification of the c-erbB-2 gene was demonstrated by Southern blotting in 1/37 grade 1, 5/32 grade 2 and 6/13 grade 3 tumours (0.005 less than P less than 0.01). Tumour 're-occurrences' were obtained from 23 of these patients on one or more occasions. Amplification was detected in re-occurrences from seven of these 23, none of whom showed amplification in the first tumour sample. DNA was also extracted from exfoliated cells in urine collected from five cases of carcinoma in situ and c-erbB-2 amplification was demonstrated in one of these. No gene amplification was identified in patients' lymphocytes, ten biopsies of normal urothelium and 22 various intravesical pathologies. Increased expression of c-erbB-2 mRNA correlated with amplification of the gene. In addition, raised levels of mRNA were seen in the absence of gene amplification in six tumours. Immunoblotting using the polyclonal antibody 21N, raised against the c-terminus of the c-erbB-2 protein demonstrated increased amounts of a 185 kD immunoreactive protein in tumours with increased c-erbB-2 gene copy number compared with control tissues. In some tumours with high c-erbB-2 gene copy number, a 155 kD immunoreactive protein not detected in controls was expressed at higher level than the 185 kD protein. Immunocytochemistry using a monoclonal antibody AB-3, raised against the c-terminus of the c-erbB-2 protein, showed a positive reaction in the cytoplasm and cell membrane of tumours with gene amplification and in 40% of tumours with no amplification. An association was found between c-erbB-2 amplification and over-expression and the development of tumour re-occurrences. We suggest that c-erbB-2 amplification and over-expression may provide a useful molecular marker in transitional cell carcinoma of the bladder and merits further investigation as a potential prognostic indicator.
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PMID:Amplification and over-expression of c-erbB-2 in transitional cell carcinoma of the urinary bladder. 167 27

Amplified expression of p185HER-2, the protein product of the HER-2/neu proto-oncogene, appears to be involved in carcinogenesis of human mammary epithelial cells. Our data suggest that an extracellular 130 Kda glycoprotein released from breast carcinoma cells may be related to the ectodomain of p185HER-2: (1) Both cellular p185HER-2 and extracellular p130, when reduced and alkylated, reacted with antipeptide antibody against the N-terminus of the HER-2 protein [alpha N(HER-21)] and reactivity was blocked by cognate peptide; (2) Neither p130 nor other extracellular proteins reacted with antiserum against the C-terminus of p185HER-2 [alpha C(HER-2)]; (3) Partial proteolysis of p185HER-2 generated an immunoreactive fragment of 130 kDa that was similar to extracellular p130; (4) Both p130 and p185HER-2 contained carbohydrate that bound to Con-A Sepharose; (5) The amount of p130 released from breast cells corresponded to the levels of expression of cellular p185HER-2. Release of the ectodomain of p185HER-2 from breast carcinoma cells may be involved in their malignant growth and may be a useful marker for assessing the expression of p185HER-2 in human tumors.
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PMID:A soluble protein related to the HER-2 proto-oncogene product is released from human breast carcinoma cells. 167 66

P185 is a receptor-like protein encoded by the neu/erbB-2 proto-oncogene. A point mutation in the transmembrane domain renders this protein oncogenic. We report here that incubation of cells with 12-O-tetradecanoylphorbol-13-acetate (TPA) stimulates the phosphorylation of the normal neu protein (p185) and the oncogenic neu protein (p185*). The increased phosphorylation occurs mainly on serine and threonine residues. Phosphate labeling experiments showed that TPA causes a reduction of basal phosphotyrosine in p185 but not p185*. Immunoblotting with antiphosphotyrosine antibody yielded similar results. TPA also inhibited tyrosine phosphorylation of p185* in an in vitro immune complex kinase assay. These data suggest that protein kinase C, the receptor for TPA, regulates p185 function through serine or threonine phosphorylation.
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PMID:TPA inhibits the tyrosine kinase activity of the neu protein in vivo and in vitro. 167 82

The c-erbB-2 proto-oncogene encodes a growth factor receptor which is over-expressed in a variety of human adenocarcinomas. Recent reports suggest that it may be of value in arriving at prognosis in breast and ovarian cancer. In this study, c-erbB-2 expression was investigated in 93 routinely processed cases of gastric carcinoma, using an immunohistochemical technique. c-erbB-2 membrane immunoreactivity was observed in 11% (10/93) of tumours, all of which were of the well differentiated intestinal type (p less than 0.01). Overall, patients with tumours expressing this proto-oncogene had a significantly improved prognosis (p less than 0.05). Within the group of intestinal-type tumours, those that were c-erbB-2-positive formed a distinct sub-population which had a better prognosis (p less than 0.02), suggesting possible differences in aetiology.
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PMID:c-erbB-2 proto-oncogene expression and its relationship to survival in gastric carcinoma: an immunohistochemical study on archival material. 167 88

The HER2 (c-erbB-2) gene encodes a protein, p185HER2, which possesses all of the structural characteristics and functional properties of a growth factor receptor, although its ligand has not yet been well characterized. HER2 is the human homolog of the rat proto-oncogene neu and is closely related to the gene encoding the epidermal growth factor receptor. Amplification of this gene and overexpression have been found to be a prognostic criterion for a 30% subpopulation of human breast cancer patients. In this study, we investigated the role of the transmembrane-spanning sequence in the biosynthesis and localization of p185HER2. A truncation mutant lacking the cytoplasmic and transmembrane domains was glycosylated and efficiently secreted. However, a mutant lacking only the transmembrane-spanning sequence was incompletely glycosylated and failed to reach the cell surface. Unexpectedly, although this deletion mutant was retained in the endoplasmic reticulum membrane, it was still able to transform NIH 3T3 cells when expressed at high levels.
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PMID:Cell transformation potential of a HER2 transmembrane domain deletion mutant retained in the endoplasmic reticulum. 168 81

With the breast carcinoma cell line BT 474 used as a source of antigen, four rat monoclonal antibodies (MAbs) (3 IgG2a and I IgA) have been prepared against the external domain of the product of the c-erbB-2 proto-oncogene. All 4 antibodies stain frozen sections of tissues that over-express the product of the c-erbB-2 proto-oncogene, and competitive binding assays showed that the antibodies recognized 2 non-overlapping epitopes. Representative antibodies from the two groups (ICR12 and 13) were shown to specifically immunoprecipitate a 190 kDa protein from 35S-methionine-labelled breast carcinoma cells where the c-erbB-2 is amplified (BT 474 and MDA-MB 361). Two of the antibodies (ICR12 and ICR17) bind to the denatured antigen in Western blots and ICR12 stains formolsaline-fixed sections of breast carcinoma tissue that over-expresses the product of the c-erbB-2 proto-oncogene. These antibodies should be useful not only for immunocytochemical diagnoses but also for radio-immunoscintigraphic and therapeutic applications.
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PMID:Rat monoclonal antibodies to the external domain of the product of the C-erbB-2 proto-oncogene. 168 75

A rapid, simple and non-toxic procedure for the simultaneous isolation of DNA and RNA from tumor tissue and cells grown in vitro is described. Guanidinium isothiocyanate was used for homogenization of tumor tissue and for cell lysis. Separation of proteins, DNA and RNA was carried out by isopycnic centrifugation in cesium trifluoroacetate. DNA was further purified by salting out residual protein. Nucleic acids prepared by this method from 47 primary human carcinomas and 17 human cell lines were analysed for amplification and expression of the HER-2/neu proto-oncogene. 2- to 10-fold amplification of HER-2/neu was noted in 7/22 mammary carcinomas (32%) and in 4/14 ovarian carcinomas (28%). No amplification of the proto-oncogene was found in 4 laryngeal carcinomas, 1 pharyngeal carcinoma, 2 retrolingual carcinomas, 3 gastric carcinomas and 1 kidney carcinoma. HER-2/neu overexpression was observed in 6/22 of mammary carcinomas (27%) and 7/14 of ovarian carcinomas (50%). No overexpression was found in all other carcinomas studied. Concordance between amplification and overexpression was noted in 3 mammary and 4 ovarian carcinomas, respectively. 3 mammary and 3 ovarian carcinomas showed overexpression without amplification. 5 human mammary carcinoma cell lines showed both amplification and overexpression of HER-2/neu. In two mammary carcinoma cell lines (MDA MB-453 and ZR 75-1) overexpression was noted without amplification of the proto-oncogene. These data combine to suggest that mechanisms other than gene amplification may also lead to overexpression of the HER-2/neu protooncogene in cancer cells.
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PMID:Determination of HER-2/neu amplification and expression in tumor tissue and cultured cells using a simple, phenol free method for nucleic acid isolation. 169 98

The epidermal growth factor receptor (EGFR) and the protein products of c-erbB-2 and c-met proto-oncogenes belong to a family of growth factor receptors with tyrosine kinase activity. In human colonic carcinomas, the expression of the EGFR and c-erbB-2 have been studied at the protein level only, while c-met expression has not been reported. We have examined the mRNA expression of these genes in human normal colorectal mucosa and primary carcinomas. The results demonstrate that the normal mucosa shows highly variable levels of EGFR and c-erbB-2 mRNAs, but expresses consistently low amounts of c-met mRNA. Colorectal carcinomas did not express significantly higher levels of the EGFR and c-erbB-2 mRNAs than the normal mucosa. In contrast, c-met was consistently and significantly overexpressed (mean sixfold) in carcinomas as compared with normal mucosa. Seventy percent of paired normal-tumor specimens showed a tumor to normal c-met mRNA ratio of greater than 4. The expression of c-met mRNA was also enhanced in the adenomas, suggesting that over-expression of this proto-oncogene may have mechanistic significance in the early stages of human colorectal carcinogenesis.
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PMID:Overexpression of c-met proto-oncogene but not epidermal growth factor receptor or c-erbB-2 in primary human colorectal carcinomas. 174 Nov 62

The transforming gene product of avian erythroblastosis virus, v-erbB, is derived from the epidermal growth factor (EGF) receptor but has lost its extracellular ligand-binding domain and was mutated in its cytoplasmic portion, which is thought to be responsible for biological signal generation. We have repaired the deletion of extracellular EGF-binding sequences and investigated the functional consequences of cytoplasmic erbB mutations. Within the resulting EGF receptors, the autophosphorylation activities of the cytoplasmic domains of v-erbB-H and v-erbB-ES4 were fully ligand dependent in intact cells. However, the mitogenic and transforming signaling activities of an EGF receptor carrying v-erbB-ES4 (but not v-erbB-H) cytoplasmic sequences remained ligand independent, whereas those of a receptor with a v-erbB-H cytoplasmic domain were regulated by EGF or transforming growth factor alpha. Thus, structural alterations in the cytoplasmic domain of growth factor receptor tyrosine kinases may induce constitutive signaling activity without autophosphorylation. These findings provide new insight into the mechanism of receptor-mediated signal transduction and suggest a novel alternative for subversion of cellular control mechanisms and proto-oncogene activation.
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PMID:Epidermal growth factor receptor cytoplasmic domain mutations trigger ligand-independent transformation. 197 19

The c-erbB-2 proto-oncogene encodes a 190 k Mr protein representing a putative growth factor receptor with considerable homology to the EGF receptor. Gene amplification and overexpression of the oncogene protein have been demonstrated in a variety of tumours including breast cancer, where it is associated with a poor prognosis. In this study we have produced and characterized a mouse monoclonal antibody, designated NCL-CB11, to the c-erbB-2 protein. NCL-CB11 was generated to a synthetic peptide sequence corresponding to a site of predicted antigenicity near the C-terminus of the internal domain of the protein. NCL-CB11 produces intense membrane-associated immunohistochemical staining in a proportion of human cancer cells. The specificity of the antibody is supported by Western blotting and immunoprecipitation studies. Reactivity with an internal site of the protein is confirmed by the necessity of cell permeabilization for reactivity in fluorescence-activated cell sorter (FACS) analysis. A high degree of correlation between immunohistochemical staining using NCL-CB11, and c-erbB-2 gene amplification has been observed. NCL-CB11 should prove to be a valuable reagent for investigations into the pathological significance of c-erbB-2 protein expression.
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PMID:NCL-CB11, a new monoclonal antibody recognizing the internal domain of the c-erbB-2 oncogene protein effective for use on formalin-fixed, paraffin-embedded tissue. 197 58


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