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)

Variability in outcome of breast carcinoma among different racial groups has been identified between Japanese and Caucasians and between Caucasians and Blacks living in the United States. These differences are not fully explained by population differences of the known prognostic variables nodal involvement and tumor hormonal receptor status. Further elucidation of the differences in outcome should include a careful examination of other prognostic variables. These include tumor size, nuclear and histologic grade, and indicators of cell proliferation (labelling index and flow cytometric measures of S phase and DNA ploidy). More recent studies indicate that growth factor regulation, oncogene amplification (HER-2/neu) and expression, and cathepsin D levels may help to further identify prognostic subgroups. A review of the literature does not provide an answer to the question of whether there are population differences in response to standard treatments. Differences in drug distribution, elimination, and metabolism which could be related to genetic or dietary factors are intriguing hypotheses to explain why differences may exist. Careful, well controlled studies to answer these questions are urgently needed.
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PMID:Response to treatment of breast cancer. 165 92

A cytogenetic analysis was performed on direct preparations and short-term cell cultures of lung tumor and normal bronchial epithelium of 19 patients carrying either a first or a second primary lung cancer. In 9 tumors (6 squamous cell carcinomas, 1 adenocarcinoma, 1 mucoepidermoid carcinoma, and 1 small cell lung carcinoma) successfully analyzed, pseudodiploid and hyperdiploid karyotypes were observed with a heterogeneous pattern of chromosome abnormalities but with a consistent involvement (5 cases) of the short or the long arm of chromosome 3. The normal bronchial epithelial cells had a normal karyotype in 11 patients, whereas in 6 patients clonal and nonclonal chromosomal abnormalities were observed. Involvement of chromosome 7 was present in 4 cases. In addition, overexpression of the growth factor receptors, epidermal growth factor receptor and HER-2/neu, was found in 9 of 18 tumors and in 6 of 13 bronchial epithelium samples. These findings suggest that early genetic lesions could be present in the normal bronchial epithelial cells that are the target of further complex and multiple genetic changes occurring during the pathogenesis of lung cancer.
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PMID:Cytogenetic abnormalities and overexpression of receptors for growth factors in normal bronchial epithelium and tumor samples of lung cancer patients. 167 Sep 93

Monoclonal antibody (MAb) 4D5 was used to analyze the phosphorylation of p185HER2, the gene product of c-erbB-2/HER2, in SK-BR-3 cells. Culture in the continuous presence of 4D5 reduced the in vivo steady-state levels of p185HER2 phosphorylation by 80% in a dose-dependent manner, suggesting that MAb 4D5 may have interfered with the activation of phosphorylation of p185HER2. The observed MAb-mediated reduction of p185HER2 phosphorylation could not be completely accounted for by down-regulation. When cultures were grown under serum-free conditions, the steady-state levels of p185HER2 phosphorylation were reduced by 56%, and addition of 4D5 further inhibited phosphorylation to 20% of steady-state levels. With continuous exposure to increasing concentrations of newborn calf serum in these cultures, there was a linear increase in tyrosine-specific phosphorylation of p185HER2, reaching a 5.4-fold increase with 10% newborn calf serum. Phosphorylation of p185HER2 in the presence of newborn calf serum was not attributable to stimulation of the epidermal growth factor receptor by epidermal growth factor or by transforming growth factor-alpha. Extension of these observations to two other mammary carcinoma cell lines. MDA-MB-453 and BT-474, also demonstrated a significant capacity of serum to induce p185HER2 phosphorylation. The demonstration of antibody-mediated partial inhibition of phosphorylation under serum-free conditions suggests that mammary carcinoma cells may also produce and secrete a factor or factors which may activate p185HER2. Our observation that growth-inhibitory MAb 4D5 is able to reduce the phosphorylation of p185HER2 by newborn calf serum and by a cellular-derived factor(s) suggests the existence of a growth factor(s) which uses phosphorylation of p185HER2 as a signal transduction pathway to regulate cell proliferation.
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PMID:Regulation of phosphorylation of the c-erbB-2/HER2 gene product by a monoclonal antibody and serum growth factor(s) in human mammary carcinoma cells. 167 Dec 97

Sections of formalin-fixed, paraffin-embedded primary salivary gland tumours were stained with a monoclonal antibody to the c-erbB-2 oncoprotein to determine the incidence and significance of expression of this protein. The series of 131 tumours comprised 33 cases of pleomorphic adenoma, 2 of malignant mixed tumour, 1 oxyphil adenoma, 31 Warthin's tumours, 4 basal cell adenomas, 6 mucoepidermoid carcinomas, 14 acinic cell carcinomas, 19 adenoid cystic carcinomas, 3 squamous carcinomas, and 18 poorly differentiated adenocarcinomas. Positive staining, as defined in previous studies, was present in five tumours (three cases of poorly differentiated adenocarcinoma, one mucoepidermoid carcinoma, and one adenoid cystic carcinoma). A review of the medical records of all patients did not disclose any clear difference between the clinical behaviour of positive and negative cases over a period of follow-up that ranged from 18 to 120 months. The findings of this study indicate that the protein product of the c-erbB-2 proto-oncogene is infrequently expressed in salivary gland tumours, and when it is localized on the tumour cell surface membrane, there is no clear evidence that this determines the biological behaviour of the tumour.
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PMID:Expression of c-erbB-2 oncoprotein in salivary gland tumours: an immunohistochemical study. 167 54

Sections of 149 breast carcinomas were examined for the over-expression of c-erbB-2 oncoprotein using the avidin-biotin immunoperoxidase technique and two different specific antibodies. These included the polyclonal antibody 21N and the monoclonal antibody 4D5. The tumours were divided into two main groups. The first included 75 cases of invasive ductal and classic invasive lobular carcinomas. The second group consisted of 74 cases with histological types known to have a good prognosis, including mucinous, alveolar variant of invasive lobular, medullary, tubular, cribriform and papillary carcinomas. Fifteen (20%) tumours of the first group were positive with the two antibodies. Fourteen of these were of the ductal type and one was a mixed invasive ductal and lobular carcinoma. Ten of the pure ductal cases had areas of comedo carcinoma. The intraductal elements in a further tumour were positively stained with 21N antibody only. None of the second group of tumours, which included histological types known to have good prognosis, stained with 4D5, although one mucinous carcinoma was positively stained with 21N. These findings suggest that in invasive breast carcinoma immunostaining for c-erbB-2 is mainly seen in a subgroup of ductal tumours, and that almost all other histological types, especially those associated with good prognosis, lack this expression.
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PMID:c-erbB-2 expression in different histological types of invasive breast carcinoma. 167 72

Correlations of c-erbB-2 protein expression with clinical outcomes of gastric carcinomas were studied in 189 gastric carcinomas. There were 23 (12.2%) carcinomas with evidence of c-erbB-2 protein in which the reaction was localized to the cell membrane. There was no significant association between c-erbB-2 staining and the macroscopic or histologic type of the carcinomas. c-erbB-2-stained tumors were more likely to be associated with serosal invasion, nodal involvement, and peritoneal metastasis, than c-erbB-2-unstained ones. In addition, c-erbB-2 was stained in none of early gastric carcinomas. The 5-year survival rates of the c-erbB-2 protein-positive and the protein-negative group were 11% and 50%, respectively. When the c-erbB-2 tissue status and seven clinicopathologic variables as conventional prognostic factors were entered simultaneously into the Cox regression model, serosal invasion, hepatic metastasis, peritoneal metastasis, nodal status, and c-erbB-2 tissue status emerged as independent prognostic variables. The results suggested that c-erbB-2 protein expression might be enhanced in advanced stages during the progression of gastric carcinoma. In this particular group of patients, immunoreactivity for c-erbB-2 protein is an indicator of poor short-term prognosis.
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PMID:Expression of c-erbB-2 oncoprotein in gastric carcinoma. Immunoreactivity for c-erbB-2 protein is an independent indicator of poor short-term prognosis in patients with gastric carcinoma. 167 70

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

Two human cell lines (UACC-812 and 893), both containing significant amplification of the HER-2/neu gene, were established from biopsy specimens of breast carcinomas. One patient had Stage II breast carcinoma; the other had metastatic disease. Characterisation of these lines has revealed that both are highly aneuploid containing multiple clonal chromosome alterations, have doubling times near 100 h, and are oestrogen and progesterone receptor negative. Electron microscopy demonstrates that both lines contain numerous microvilli, cytoplasmic filaments, multivesicular bodies, and desmosomes. Immunoblot analysis for P-glycoprotein using the monoclonal antibody C219 was negative for both patient cell lines. These relatively rare cell lines may represent a useful model to investigate human breast carcinomas.
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PMID:Establishment of two new cell lines derived from human breast carcinomas with HER-2/neu amplification. 167 77

Using the 21N polyclonal antibody, we immunohistochemically stained 314 primary breast carcinomas to identify those tumors overexpressing the c-erbB-2 oncoprotein and to ascertain the prognostic significance of this expression on disease-free and overall survival. Positive membrane staining was present in 52 (17%) of these carcinomas of which 7 (13%) were ductal carcinomas in situ. There was no significant relationship between c-erbB-2 positivity and (a) age at diagnosis, (b) menopausal status, (c) tumor size, (d) lymph node status, (e) estrogen receptor status, or (f) whether or not the patient had disseminated disease outside the axillary fields. However, c-erbB-2-positive tumors were significantly associated with poorer grade (P = 0.02). Patients who were positive for this oncoprotein had a shorter disease-free survival (P = 0.002) and reduced overall survival (P = 0.0001). Overexpression of this oncoprotein was predictive of a worse prognosis in lymph node-positive disease (P = 0.003) and in patients presenting with grade II tumors (P = 0.001). Stratifying the patients on the basis of estrogen receptor status suggested that c-erbB-2+/estrogen receptor-negative status was predictive of a poorer prognosis when compared with the other subgroups (P less than 0.001). Primary and recurrent tumor tissues were available from 42 of the 314 patients. Identical patterns of c-erbB-2 expression occurred in 95% of cases, arguing against a direct role for c-erbB-2 expression in the process of tumor dissemination. The high incidence of staining in ductal carcinomas in situ suggests that expression of this oncoprotein is an early event in tumorigenesis. Finally, multivariate analysis indicated that the c-erbB-2 oncoprotein was an independent prognostic indicator for overall survival in breast carcinoma patients.
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PMID:Prognostic significance of c-erbB-2 and estrogen receptor status in human breast cancer. 167 98

Lobular carcinoma in situ (LCIS) has uncertain malignant potential; biologic markers that will identify patients at risk for a poor clinical outcome have been sought actively. Amplification of the c-erbB-2 protooncogene has been correlated with poor prognosis in invasive mammary carcinoma, and immunohistochemical evaluation for expression of the oncogene protein has been correlated with gene amplification. The authors retrospectively evaluated 62 cases of lobular neoplasia for expression of the c-erbB-2 gene product on formalin-fixed, deparaffinized sections, using two monoclonal anti-erbB-2 (p185) antibodies (c-neu Ab3 and m-erb) and one polyclonal anti-erbB-2 antibody (pAb 1) by the avidin-biotin-peroxidase method. All 62 cases were negative with the pAb 1 antibody; one of 62 cases was weakly positive with the c-neu Ab3 in a membranous pattern. Expression of c-erbB-2 gene product was identified on adjacent invasive ductal carcinoma in one case and in adjacent ductal carcinoma in situ in another. None of 15 cases if infiltrating lobular carcinoma was positive with either of the two anti-c-erbB-2 antibodies. Strong positivity was found on benign epithelium in one case, demonstrating epitheliosis. In summary, evidence of expression of the c-erbB-2 gene product was found in one of 57 cases of LCIS and none of 15 cases of invasive lobular carcinoma. This suggests that, in contrast to reported data concerning intraductal and invasive ductal carcinoma, c-erbB-2 oncogene amplification and/or overexpression does not play a significant role in the progression of lobular breast neoplasia.
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PMID:C-erbB-2 oncogene protein in in situ and invasive lobular breast neoplasia. 167 30


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