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 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

In this review I summarize the experimental data in favor of the notion that control of epidermal growth factor (EGF) receptor (R) and/or c-erbB-2 protooncogene expression by specific autocrine growth factors and certain classical endocrine hormones serves as a transducer of extracellular signals that ultimately lead to growth responses in breast carcinoma cells. I summarize some new results on the role of epidermal growth factor (EGF), transforming growth factor (TGF) alpha, and TGF beta in the control of EGF-R protooncogene expression in human breast carcinoma cells. Furthermore, the data embracing the hypothesis that the growth actions of hormone receptors that are homologous to the v-erbA oncogene (estrogens, progesterone, thyroid hormones, retinoic acid, and vitamin D) are mediated, in part, by modulating EGF-R and/or c-erbB-2 protooncogene transcription are reviewed. Finally, I develop the theme that cooperation of certain c-erb-A-related, c-erbB-2 and/or EGF-R gene products contribute to the uncontrolled growth of human mammary carcinoma cells. From the evidence reviewed, one can infer that elucidation of the molecular control of EGF-R/c-erbB-2 gene expression by c-erbA-related gene products may lead to both a better understanding of breast carcinogenesis and a new therapeutic approach directed at controlling the transcriptional responses of EGF-R/c-erbB-2 genes.
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PMID:Modulation of EGF receptor protooncogene expression by growth factors and hormones in human breast carcinoma cells. 167 74

Material from 41 patients with primary breast carcinoma and lymph node metastases at the time of primary surgical intervention was immunostained for c-erbB-2 protein, neuron-specific enolase (NSE), and estrogen receptors. Thirty of the primary breast carcinomas were of ductal type. Six were classified as infiltrating lobular carcinomas, 2 were apocrine, 1 was mucinous, and 1 was a tubular carcinoma. One tumor could not be classified as ductal or lobular by light microscopic examination alone. The number of lymph node metastases available varied from 1 to 14 per case (median, 3.9). Nine (22%) of the primary breast carcinomas (8 ductal and 1 apocrine) expressed c-erbB-2 protein and showed c-erbB-2 gene amplification; 12 expressed NSE immunoreactivity. None expressed both markers. Estrogen receptor immunoreactivity was present in 23 of the 41 cases, including 9 of the NSE-positive cases. C-erbB2- protein-positive metastases were present in 18 cases (44%), and in 13 cases all metastases were immunostained. In 5 cases the expression of c-erbB-2 protein varied from metastasis to metastasis. NSE immunoreactivity was expressed in 10 cases, and in 3 cases with minor NSE-positive cell populations the metastatic lesions expressed c-erbB-2 protein as well. All 9 primary breast carcinomas expressing c-erbB-2 protein had lymph node metastases with c-erbB-2-immunoreactive tumor cells. Eight of the 9 c-erbB-2 protein-negative primary tumors with metastases expressing c-erbB-2 protein showed no amplification of the c-erbB-2 gene.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The c-erbB-2 protein in primary and metastatic breast carcinomas. 167 62

We examined samples of tumors of human breast, ovary, and colon of various degrees of malignancy for the expression of p53 protein, using a panel of anti-p53 antibodies and peroxidase immunohistochemistry. Of 66 tumor cases (24 cases of ovarian carcinoma, 23 cases of colon adenocarcinoma, and 19 cases of breast carcinoma), 36 (53%) showed high levels of expression of p53 using a human-specific antibody, and 16 (24%) showed high expression of a mutant form of p53. In the mutant p53-positive breast tumor samples, six (86%) were positive for HER-2/neu reactivity, compared with colon (0/4) and ovarian tumors (1/5). The pattern of p53 intracellular localization and tissue distribution, and the relationship between the expression of mutant p53 and cell differentiation, were also examined; poorly differentiated cells showed either overexpression of p53 or higher levels of mutant p53 in comparison with more normal cells.
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PMID:Immunohistochemical analysis of p53 and HER-2/neu proteins in human tumors. 168 Aug 97

P-glycoprotein and epidermal growth factor (EGF) receptor expression were surveyed immunohistochemically in the tissue of urogenital carcinomas including 12 renal cell carcinomas, 9 bladder transitional cell carcinomas, 2 prostate adenocarcinomas and 1 penile squamous cell carcinoma. Three bladder carcinomas and the penile carcinoma were following initial chemotherapy at the time of relapse. P-glycoprotein expression was detected in 3 of 12 renal cell carcinomas and in all recurrent carcinomas. EGF receptor was not detected in any of the specimens.
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PMID:Detection of P-glycoprotein in human urogenital carcinomas and its relationship to epidermal growth factor receptor expression. 168 34

A sandwich radioimmunometric assay using monoclonal antibodies 6G10 and SV2-61 gamma directed to the extracellular domain of the c-erbB-2 oncogene product was developed and the antigen levels in sera from normal donors and patients with breast carcinoma were determined. The antigen levels in normal donors were uniformly low (9.52 +/- 0.91 ng/ml) and 3.0% (2/66 cases) slightly exceeded the cutoff value (11.4 ng/ml). In patients with breast carcinoma, serum c-erbB-2 protein levels increased and the positivity was as high as 45.7% (16/35 cases) in recurrent cases. Determination of c-erbB-2 protein may be a useful marker for serological diagnosis of breast carcinoma.
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PMID:[Development of sandwich radioimmunometric assay for serum c-erbB-2 oncogene product and its significance in diagnosing breast carcinoma]. 168 26

The overexpression of the c-erbB-2 oncoprotein is now thought by most authors to be associated with adverse prognosis in breast carcinoma. In this study, we investigate the relationship between overexpression of the c-erbB-2 oncoprotein and nuclear size by morphometry in a series of 150 human breast carcinomas, comprising 65 cases of ductal carcinoma in situ (DCIS) and 85 cases of invasive adenocarcinoma. The mean nuclear size for c-erbB-2 positive cases of DCIS was 54.8 micron 2 and invasive carcinoma was 52.1 micron 2 respectively, in contrast with 41.6 micron 2 and 42.5 micron 2 for c-erbB-2 negative cases of DCIS and invasive carcinoma respectively. Flow cytometric examination of DNA in a subset of 91 of these tumours showed no association between tumour cell aneuploidy and c-erbB-2 overexpression. S-phase fraction could be calculated on 20 cases of DCIS and 48 invasive carcinomas. There was a strong association between c-erbB-2 overexpression, S-phase fraction (p less than 0.001) and proliferative index (p less than 0.001) in 20 cases of DCIS. A weak association of S-phase fraction and c-erbB-2 overexpression was seen in 48 invasive carcinomas (p = 0.047). This study confirms the subjective impression that there is a relationship between large tumour cell nuclear size and an overexpression of the c-erbB-2 oncoprotein, and also shows an association with increased tumour cell proliferation.
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PMID:Nuclear and flow cytometric characteristics associated with overexpression of the c-erbB-2 oncoprotein in breast carcinoma. 168 5

Staurosporine is a potent microbial inhibitor of a number of protein kinases, including protein kinase C, cyclic AMP-dependent kinase, and the tyrosine kinase pp60src. We have used staurosporine to investigate the role of phosphorylation in the regulation of the epidermal growth factor (EGF) receptor in both human epidermal carcinoma A431 cells and mouse Swiss 3T3 fibroblasts. We report here that staurosporine treatment causes enhancement in high affinity EGF binding and a decrease in the phosphorylation state of the unstimulated receptor at a number of residues, including threonine 669. Staurosporine also antagonizes the inhibition of high affinity EGF binding and the increase in phosphorylation state of the unstimulated EGF receptor by phorbol esters and the calcium ionophore A23187. Staurosporine is an effective inhibitor of the EGF-stimulated receptor tyrosine kinase in vitro and thus does not enhance EGF stimulation of EGF receptor autophosphorylation in vivo. These results suggest that phosphorylation plays a major role in the regulation of the high affinity binding state of the EGF receptor in both unstimulated and mitogenically activated cells.
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PMID:Regulation of the epidermal growth factor receptor by growth-modulating agents: effects of staurosporine, a protein kinase inhibitor. 168 32

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


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