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)

Activation of the c-erbB-2 oncogene can occur by amplification of c-erbB-2 DNA and by overproduction of c-erbB-2 mRNA and c-erbB-2 protein. Approximately 20 percent of breast carcinomas show evidence of c-erbB-2 activation, which correlates with a poor prognosis primarily in patients with metastasis to axillary lymph nodes. Studies that have attempted to correlate c-erbB-2 activation with other prognostic factors in breast carcinoma have reported conflicting conclusions. The pathologic and clinical significance of c-erbB-2 activation in other neoplasms is unclear and should be assessed by additional studies.
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PMID:Clinical and pathologic significance of the c-erbB-2 (HER-2/neu) oncogene. 134 51

Sixty-eight patients with advanced breast cancer were treated with mitoxantrone and clinical responses assessed. Expression of c-erbB-2 protein and cytosolic glutathione S-transferase (GST) isoenzymes pi, alpha and mu by the primary tumours of these patients was determined immunohistochemically, and correlated with treatment response. Tumours overexpressing c-erbB-2 (n = 16, 23%) showed a lower response rate (50% vs 58%) and shorter duration of response to treatment, compared with c-erbB-2 negative tumours. These associations were not statistically significant but survival following start of treatment was significantly shorter in the c-erbB-2 positive group. For each GST isoenzyme, the response rate and duration of response of the group showing enzyme expression did not differ significantly from those with negatively staining tumours. These data do not support a role for expression of GSTs alone in resistance to mitoxantrone monotherapy in advanced breast cancer. The poorer post treatment survival of patients with c-erbB-2 positive tumours suggests they could be selected for more intensive treatment regimens.
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PMID:Response to mitoxantrone in advanced breast cancer: correlation with expression of c-erbB-2 protein and glutathione S-transferases. 134 48

The expression of cytosolic glutathione S-transferase (GST) isoenzymes has been assessed in a series of 74 primary human breast carcinomas using an immunohistochemical method. GST pi was detected in sections from all 74 tumours; it was expressed by non-epithelial (stromal and inflammatory) cells in 62 tumours (84 per cent), but by tumour epithelium in only 35 (47 per cent). Non-neoplastic mammary epithelium was uniformly positive for GST pi. Expression of GST alpha and mu was observed in 19 and 42 per cent of the tumours, respectively, and was largely confined to the neoplastic component. Lack of staining of tumour epithelium for GST pi was significantly associated with poorer tumour differentiation (higher grade). There was no association between expression of any of the three isoenzymes and either menopausal status or expression of c-erbB-2 oncogene protein product. Immunohistochemistry is a useful method for the investigation of expression and cellular localization of GSTs within tumours; such data are needed to improve our understanding of the role of these enzymes in neoplasia and in resistance to cytotoxic drug therapy.
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PMID:Immunohistochemical demonstration of glutathione S-transferases in primary human breast carcinomas. 134 80

A total of 52 intraductal carcinomas were classified according to nuclear size and histologic subtype and immunostained for neuron-specific enolase (NSE) and c-erbB-2 oncoprotein. Eleven out of 13 cases of the large cell comedo variant of intraductal carcinoma exhibited strong c-erbB-2 protein immunoreactivity, while only one was NSE positive. Nineteen out of 23 intraductal carcinomas of small cell type exhibited NSE immunoreactivity. None of these was c-erbB-2 protein positive. Some 72% of NSE positive cases were also immunoreactive for other neuroendocrine screening markers and/or hormones. We conclude that there is an inverse relationship between NSE immunoreactivity and c-erbB-2 protein expression in intraductal carcinomas.
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PMID:C-erbB-2 protein and neuroendocrine expression in intraductal carcinomas of the breast. 134 23

To develop an efficient strategy for the targeting of anti-tumor effector cells, we prepared bispecific antibody (BsAb) containing anti-CD3 and an anti-c-erbB-2 proto-oncogene product. The prepared BsAb specifically reacts with both c-erbB-2-positive tumor cells and CD3+ CTL. Human CD4+ helper/killer T cells, induced from peripheral-blood mononuclear cells by activation with immobilized anti-CD3 monoclonal antibody (MAb) plus IL-2, showed no significant cytotoxicity against tumor cells. However, treatment of human CD4+ helper/killer cells with the BsAb caused the induction of specific cytotoxicity against c-erbB-2-positive tumor cells. CD4+ helper/killer cells also produced significant amounts of IL-2 during co-culture with c-erbB-2-positive tumor cells in the presence of the BsAb. Moreover, by combination with the BsAb, CD4+ helper/killer cells showed a strong in vivo anti-tumor effect against c-erbB-2 transfectant or human colon-cancer cells implanted in nude mice. Our results strongly suggest that the c-erbB-2 proto-oncogene product on human tumor cells may be a good target for BsAb-directed adoptive tumor immunotherapy.
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PMID:Human c-erbB-2 proto-oncogene product as a target for bispecific-antibody-directed adoptive tumor immunotherapy. 134 16

To gain insight into the mechanisms which control the mitogenic response to epidermal growth factor (EGF), we have partially purified and characterized several intracellular proteins which are phosphorylated on tyrosine residues following activation of the epidermal growth factor receptor (EGFR). Partial purification was achieved by immunoaffinity chromatography using immobilized anti-phosphotyrosine antibodies. Antisera generated against the partially purified proteins were used to identify at least five novel EGFR putative substrates, designated, on the basis of their apparent molecular weight, p97, p68, p61, p56, and p23. All of these proteins became specifically phosphorylated on tyrosine after EGF treatment of intact cells, as assessed by phosphoamino acid analysis, and none of them represented an EGFR degradation product. The phosphorylation of these proteins appeared to be relatively specific for the EGFR. In particular, an EGFR-related kinase, erbB-2 was much less efficient than EGFR at phosphorylating p97, p56, and p23 and incapable of phosphorylating p68. The identification of these novel EGFR putative substrates should lead to a better understanding of the mechanisms controlling the specificity of EGFR-mediated mitogenic signaling.
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PMID:Identification and biochemical characterization of novel putative substrates for the epidermal growth factor receptor kinase. 134 29

The expressions of epidermal growth factors (EGF), epidermal growth factor receptors (EGFR), and the c-erbB-2 oncoprotein were immunohistochemically examined in 25 cases of human pancreatic carcinoma and epineoplastic pancreatitis and in 10 non-cancerous/non-inflammatory pancreatic tissues. The positive rates of EGF, EGFR, and the c-erbB-2 oncoprotein in cancer tissues were 72%, 36%, and 28%, respectively. EGF was stained mainly in the cytoplasm and partly on the surfaces of the cancer cells. EGFR and the c-erbB-2 oncoprotein were stained mainly on the surfaces of the cancer cells and partly in the cytoplasm. The expressions of these 3 products correlated significantly with tumor invasion into the anterior and posterior areas surrounding the pancreas. In the EGF, EGFR, and c-erbB-2 positive cancer tissues, some stromal cells, that is fibroblasts and endothelial cells, were also positive. In the adjacent pancreatic tissues with inflammation, these products were noted in some ductal cells, acinar cells, fibroblasts and endothelial cells. No distinct staining was detected in non-cancerous/non-inflammatory tissues. The survival period for patients who tested positive for these three proteins was statistically shorter than for those who tested negative. These results suggest that the coexpression of EGF and EGFR and the expression of the c-erbB-2 oncoprotein are related to the existence of the invasion of human pancreatic cancer. Furthermore, an immunohistochemical examination of these three products is useful in forming a prognosis for pancreatic cancer patients.
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PMID:The immunohistochemical expressions of epidermal growth factors, epidermal growth factor receptors and c-erbB-2 oncoprotein in human pancreatic cancer. 134 73

The control of expression of the erbB-2 protein was examined in two mammary epithelial cells lines, HC11 and 31E. The erbB-2 protein content varied dramatically depending upon cell density and upon the presence of epidermal growth factor (EGF) in the culture medium. The changes in protein content were not due to variation in the erbB-2 mRNA level. Analysis of the metabolic turnover of the erbB-2 protein showed that its rate of degradation was two- to threefold higher in cells growing at low density than in cells confluent for 2 days. The addition of EGF to the culture medium caused an increase in the phosphoamino acid content and an increase in the turnover of the erbB-2 protein. Cell fractionation experiments were performed, and a shift in the cellular localization of the erbB-2 protein towards the lysosomal compartment in EGF-treated HC11 cells was found. This is reflected by an increase in the degradation rate of the erbB-2 protein. These findings suggest that in mammary epithelial cells the stability of the erbB-2 protein is an important regulatory control point in determining the level of the protein. The degradation rate is sensitive to cell confluency and is controlled by EGF receptor activity.
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PMID:Surface expression of erbB-2 protein is post-transcriptionally regulated in mammary epithelial cells by epidermal growth factor and by the culture density. 134 17

The erbB-2 oncogene encodes a 185-kDa transmembrane protein that has been suggested to be a growth factor receptor. We have previously identified and purified a 30-kDa growth factor (gp30) that is a ligand for the p185erbB-2 protein that at high concentrations induces growth inhibition of cells with erbB-2 amplification. We now report the purification and characterization of a protein from SKBr-3 human breast cancer cells with a molecular mass of 75 kDa (p75) that is a p185erbB-2 ligand. An affinity column coupled to the extracellular domain of p185erbB-2 was used for the purification. We found that p75 induced tyrosine phosphorylation of the erbB-2 oncoprotein, as determined by in vivo and in vitro phosphorylation and phosphoamino acid analysis. p75, as well as gp30, stimulated cell proliferation and colony formation of cells overexpressing erbB-2. The specificity of this effect was confirmed by showing that the antiproliferative effects of soluble erbB-2 extracellular domain were reversed by either p75 or gp30. p75 did not show binding to the epidermal growth factor receptor and had no growth effects on cells overexpressing epidermal growth factor receptor. These data show that SKBR-3 cells, which exhibit erbB-2 amplification and overexpression, secrete a growth factor that binds and activates p185erbB-2 specifically.
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PMID:Characterization of a growth factor that binds exclusively to the erbB-2 receptor and induces cellular responses. 134 47

The association of c-erbB-2 gene amplification product (p185) with histologic tumor type in 100 patients with primary breast cancer was determined. In 49 patients with infiltrating ductal carcinoma p185 detection was correlated with histologic findings (tumor grade, lymphnode status, receptor status). Strong positive staining for p185 protein was found in 10 patients (20%) with infiltrating ductal breast carcinoma and correlated with complete negative estrogen/progesterone receptor status and with histologic grade G3. There was neither an association with lymphnode involvement nor was there any to negative estrogen and progesterone receptor status alone. At present, we cannot say whether or not there is a correlation between the degree of c-erbB-2 gene amplification and prognosis. Follow-up studies are necessary to determine whether c-erbB-2 gene amplification allows definition of a specific subset of women who could benefit from adjuvant therapy.
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PMID:Correlation of c-erbB-2 protein expression with histologic grade, lymph node involvement and steroid receptor status in human breast tumors. 134 86


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