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)

K1 is a murine monoclonal antibody (MAb) derived from a hybridoma generated by the fusion of splenocytes of BALB/c mice immunized with a human ovarian tumor cell line, OVCAR-3. This antibody reacts strongly with epithelial ovarian tumors and mesotheliomas. The antigen recognized by MAb K1, designated CAK1, has recently been characterized as a 40-kDa protein probably anchored to the cell surface by glycosyl-phosphatidylinositol. Using immunoperoxidase histochemical methods, we examined 37 squamous-cell carcinoma (SqCC) samples from cervix, lung, esophagus and other origins, and 12 normal squamous epithelia of the cervix and esophagus for their reactivity with MAb K1. Of the SqCC specimens, 81% showed K1 reactivity with variable intensity, but none of 12 normal tissue samples of squamous epithelia did so. Two patterns of CAK1 expression in tumor samples were found, i.e., a heterogeneous pattern with strong intensity, and a homogeneous pattern with weak intensity. Three carcinomas in situ of the larynx, vulva and esophagus were moderately positive with K1, suggesting that CAK1 antigen may occur in the early stage of carcinogenesis of SqCC. The expression of CAK1 was also compared with expression of CA125, HER-2/neu, p53 and P-glycoprotein, and MAb K1 was found to react most consistently with SqCC. Since K1 reacts with a majority of cervical and esophageal carcinomas but has no detectable reactivity in normal epithelia of the cervix uteri and esophagus, MAb K1 could be of value as a reagent to help distinguish between normal and neoplastic cells on sections as well as in cytological samples.
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PMID:Frequent expression of the tumor antigen CAK1 in squamous-cell carcinomas. 135 Oct 45

c-erbB-2 protein expression was investigated immunohistochemically in frozen thyroid tissue specimens from 42 patients using a polyclonal sheep antibody. c-erbB-2 immunoreactivity was detected in 12 out of 17 papillary carcinomas, while no c-erbB-2 protein immunostaining was seen in cases of follicular adenoma (five cases), follicular carcinoma (five cases) or medullary carcinoma (one case), nor in cases of non-neoplastic tissue, including normal thyroid tissue from tumour-bearing glands. RNA was extracted from 51 thyroid tissue samples from 34 of the above patients, and c-erbB-2 mRNA was analysed by slot-blot hybridisation. c-erbB-2 mRNA was detectable in all samples, but papillary carcinomas and lymph node metastases showed significantly higher levels of c-erbB-2 mRNA compared to non-neoplastic tissue. The present demonstration of positive c-erbB-2 immunostaining in papillary thyroid carcinomas is contradictory to previous findings on formalin-fixed, paraffin-embedded material, and emphasises the importance of tissue quality for c-erbB-2 protein detection.
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PMID:Expression of c-erbB-2 protein in papillary thyroid carcinomas. 135 25

In order to analyze the correlation between immunohistochemical positivity for c-erbB-2 oncoprotein and prognosis in patients with malignant salivary gland tumors, 59 cases of malignant tumors of the major salivary glands, including 35 parotid gland, 20 submaxillary gland and 4 sublingual gland tumors, were studied immunohistochemically using a polyclonal antibody against c-erbB-2 oncoprotein. Positive staining was observed in 13 (22%) of the 59 cases. Interestingly, positive results were obtained only in adenocarcinoma (6/20) and carcinoma in pleomorphic adenoma (7/15), and not in any other histological types such as adenoid cystic carcinoma, mucoepidermoid tumor, and squamous cell carcinoma. There was no correlation between the degree of differentiation of adenocarcinoma and c-erbB-2 positivity. Since the carcinoma in pleomorphic adenoma positive for c-erbB-2 oncoprotein was adenocarcinoma, adenocarcinoma and adenocarcinoma in pleomorphic adenoma were placed together (n = 33), and the presence or absence of c-erbB-2 oncoprotein in this group was examined for correlation with patients' survival and other clinicopathological features, including clinical stage, tumor size, surgical margins, and lymph node status. The c-erbB-2-positive tumors tended to be more advanced and larger than negative tumors. Similarly, c-erbB-2-positive tumors were difficult to resect completely, were associated with lymph node metastasis more frequently, and showed lower disease-free survival than negative cases (P less than .05). We conclude that immunohistochemical positivity for c-erbB-2 is an indicator of aggressiveness in both adenocarcinoma and adenocarcinoma in pleomorphic adenoma of the major salivary glands.
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PMID:Immunohistochemical study of c-erbB-2 oncoprotein overexpression in human major salivary gland carcinoma: an indicator of aggressiveness. 135 53

The overexpression of the proto-oncogene HER-2 (c-erbB-2/neu) in ovarian and mammary carcinoma is an important indicator for a bad prognosis. In this study we demonstrate that in 7 out of 8 ovarian carcinoma cell lines there is an interferon-gamma-mediated reduction in HER-2 specific protein, and this effect was found to correlate with the antiproliferative action. It is interesting to note that there is no relationship between the absolute amount of HER-2 protein expressed and the sensitivity of the ovarian carcinoma cells for an antiproliferative activity of interferon-gamma. Other chemotherapeutic agents did not affect HER-2 expression although they inhibited the proliferation. The oncogene expression was lowered only in the ovarian carcinoma cell lines and not in 3 interferon-gamma sensitive human breast cancer cell lines. Expression of the oncogene HER-2 is the leading prognostic factor in ovarian cancer. Its modulation might represent a mechanism by which interferon-gamma inhibits cell proliferation.
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PMID:[Interferon-gamma suppresses expression of the HER-2 oncogene in ovarian cancer cells]. 135 79

The expression of p53 protein, oestrogen receptor protein, epidermal growth factor receptor (EGFR) and overexpression of the c-erbB-2 oncoprotein was examined in a series of 149 primary symptomatic breast carcinomas. Expression of p53 was present in 62 of 146 cases (42.5%) of the invasive carcinoma and one of three cases (33.3%) of ductal carcinoma in situ (DCIS) examined. Statistical associations of tumour oestrogen receptor positivity and lack of p53 protein expression, chi 2 = 19.78 (d.f. = 1), P less than 0.001, positive tumour p53 status and poor tumour grade; chi 2 = 14.1 (d.f. = 2), P less than 0.001, EGFR expression chi 2 = 7.07, (d.f. = 1), P less than 0.01 and tumour c-erbB-2 protein overexpression; chi 2 = 4.61 (d.f. = 1), P = 0.032 were identified. Expression of p53 is rare in invasive lobular carcinoma of classical type (8.3% of cases examined) in contrast to other common types of mammary carcinoma. Non-significant trends of p53 protein expression and increased regional tumour recurrence; chi 2 = 3.20 (d.f. = 1), P = 0.074 and also poorer patient survival; chi 2 = 3.76 (d.f. = 1), P = 0.053 were identified. p53 protein expression is a common event in human breast cancer and is present in both DCIS and invasive mammary carcinoma. Abnormal expression of p53 protein is a feature of both in situ and invasive breast carcinoma, implying that the abnormal p53 protein expression may be implicated in the early stages of mammary carcinoma progression.
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PMID:p53 protein expression in human breast carcinoma: relationship to expression of epidermal growth factor receptor, c-erbB-2 protein overexpression, and oestrogen receptor. 135 62

Over-expression of the proto-oncogene HER-2 (c-erbB-2/neu) in ovarian, endometrial, and mammary carcinoma is an indicator of poor prognosis. Interactions between the epidermal growth factor (EGF) receptor and the HER-2 protein have been described. The aim of this study was to elucidate the effects of EGF on HER-2 expression. In the human ovarian carcinoma cell lines HTB-77, OVCAR-3, 2780, SKOV-6, SKOV-8 and 2774, and the human mammary tumor cell line SKBR-3, total cellular p185HER-2 was determined by an ELISA, whereas the surface p185HER-2 was measured with a living-cell RIA. Stimulation of these cell lines with either EGF (0.1-30 nM) or TGF-alpha (0.1-30 nM) led to a significant reduction in p185HER-2 expression. The effect was more pronounced in cells with normal HER-2 expression. A reduction of mRNA levels for p185HER-2 by EGF was observed in OVCAR-3 cells but not in the over-expressing lines HTB-77 and SKBR-3. Interestingly, the EGF-induced effect was not always associated with growth stimulation and was not correlated with the number of EGF binding sites detected by a radioligand assay. Our data indicate that EGF treatment results in a down-regulation of p185HER-2.
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PMID:Epidermal growth factor reduces HER-2 protein level in human ovarian carcinoma cells. 135 58

In the present study we have analyzed the effect of a synthetic protein kinase C (PKC) activator 3-(N-acetylamino)-5-(N-decyl-N-methylamino)-benzyl alcohol (ADMB) and the natural PKC-activating tumor-promoting agents 12-O-tetradecanoylphorbol 13-acetate (TPA) and mezerein on the antigenic phenotype of T47D human breast carcinoma cells. All three agents increased the surface expression of the tumor-associated antigen BCA 225 and various cellular antigens, including HLA class II antigens, intercellular adhesion molecule 1 (ICAM-1) and c-erbB-2. Expression of the same antigens was also upregulated to various extents in T47D cells by recombinant fibroblast (IFN beta) and immune (IFN gamma) interferon. Shedding of BCA 225 from T47D cells was induced by TPA, mezerein, IFN beta and IFN gamma, whereas ADMB did not display this activity. The ability of ADMB, TPA and mezerein to modulate the antigenic phenotype of T47D cells appears to involve a PKC-mediated pathway, since the PKC inhibitor, H-7, eliminates antigenic modulation. In contrast, the ability of IFN beta and IFN gamma to enhance the synthesis, expression and shedding of BCA 225, as well as to enhance HLA class II antigens, c-erbB-2 and ICAM-1 expression, was either unchanged or modestly reduced by simultaneous exposure to H-7. Analysis of steady-state mRNA levels for HLA class I antigens, HLA class II-DR beta antigen, ICAM-1 and c-erbB-2 indicated that the ability of H-7 to inhibit expression of these antigens in TPA-, mezerein- and ADMB-treated cells was not a consequence of a reduction in the steady-state levels of mRNAs for these antigens. The results of the present investigation indicate that the biochemical pathways mediating enhanced antigenic expression in T47D cells induced by TPA, mezerein and the synthetic PKC activator ADMB are different from those induced by recombinant interferons. Furthermore, up-regulation of antigenic expression in T47D cells can occur by a PKC-dependent or a PKC-independent pathway.
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PMID:Modulation of the antigenic phenotype of human breast carcinoma cells by modifiers of protein kinase C activity and recombinant human interferons. 135 26

Abnormalities of epidermal growth factor receptor (EGFR) and c-erbB-2 have been demonstrated to be correlated with aggressive biologic behavior in a variety of human cancers. To analyze the possible roles of these oncogenes in ovarian neoplasms, immunolocalization of EGFR and c-erbB-2 oncogene product was performed in 45 cases of human ovarian mucinous and serous cystadenomas, carcinomas of low malignant potential (LMP), and invasive carcinomas by employing antibodies against these oncogene products. EGFR immunoreactivity was present in 15 of 35 LMP and invasive carcinomas and 1 of 10 cystadenomas. On the contrary, immunoreactivity of p185, which is an oncogene product of c-erbB-2, was detected only in five cases of carcinoma and in no benign cystadenoma. These results indicate that EGFR may be involved in the neoplastic process in epithelial ovarian adenocarcinoma, especially mucinous carcinoma, but involvement of c-erbB-2 is probably not as prevalent as considered previously. Four of the five cases immunohistochemically positive for p185 were also positive for EGFR, which suggests that expression of EGFR and p185 is to some extent correlated in human ovarian carcinoma.
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PMID:Immunolocalization of epidermal growth factor receptor and c-erbB-2 oncogene product in human ovarian carcinoma. 135 38

In breast cancer the tumor stage, axillary lymph node metastases and hormone receptors are well established prognostic factors. Nevertheless, additional prognostic factors are still desirable. Recently, attention has focussed on molecular markers, in particular mutated genes involved in the pathogenesis of breast carcinoma. The first such marker to be tested for its clinical relevance has been the c-erbB-2 oncogene. However, the results of the many studies published on this subject are controversial. Further progress can be expected from two different strategies. The molecular pathogenesis of breast cancer must be elucidated in more detail, since it is likely that breast cancer is the result of a progressive accumulation of many different somatic mutations in diverse genes such as oncogenes and tumor-suppressor genes. Rather than relying on retrospective analyses, the clinical relevance of new markers must be tested in prospective clinical trials.
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PMID:[Current molecular prognostic factors in breast carcinoma]. 135 43

Monoclonal anti-proliferating cell nuclear antigen (PCNA PC10), which is directed against a 36 kDa auxiliary protein for DNA polymerase delta specific for the S-phase of cell cycle, was used to measure tumour cell proliferation in 4 lactating breasts and 98 benign and malignant breast tumours. The percentage of PCNA-positive cells determined by point counting was significantly lower in the lactating breast [mean 3.6%, standard deviation (SD) 0.67, n = 5] than in fibroadenoma and mastopathy (mean 23.7, SD 5.0, n = 2). Primary breast carcinoma showed a PCNA index ranging from 2% to 36% (mean 12.3, SD 9.3, n = 50), whereas in recurrent carcinoma the index was mean 28.5, SD 4.0. A high index was correlated with c-erbB-2 and epidermal growth factor (EGF) receptor membrane reactivity, worsening histological grade, poor survival and disease-free survival. The expression of c-erbB-2 and EGF receptor was associated with poor survival and disease-free survival in primary breast cancer patients.
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PMID:Proliferating cell nuclear antigen in breast lesions: correlation of c-erbB-2 oncoprotein and EGF receptor and its clinicopathological significance in breast cancer. 135 12


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