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)

Differences in the immunohistochemical expression of Cathepsin D, C-erbB-2 protein (p185), and growth fraction (MIB-1) in glandular and squamous epithelium in adenocarcinoma of endometrioid subtype were studied together with Cathepsin D in macrophages. The findings were correlated with conventional prognostic parameters. A search for human papilloma virus (HPV) (probes 6/11, 16/18, and 31/33/51) by in situ hybridization was also performed. Formalin-fixed and paraffin-embedded tissues from 61 adenocarcinomas with > 10% squamous epithelium were studied. MIB-1 was very low in squamous epithelium, no correlation was found between MIB-1 in squamous and glandular epithelium, and only the glandular epithelium correlated with depth of invasion and stage, indicating that glands are most important with regard to prognosis. Cathepsin D expression in macrophages was significantly increased in advanced stage and may be of prognostic value, but more studies on tissue sections are needed to evaluate the relationship between its expression in tumor cells and other cells. p185 showed no value as a prognosticator. Finally, our study found HPV infrequently in endometrial carcinomas.
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PMID:Endometrial adenocarcinoma of endometrioid subtype with squamous differentiation: an immunohistochemical study of MIB-1 (ki-67 paraffin), cathepsin D, and C-erbB-2 protein (p185). 860 74

Recent studies suggest that aberrations of c-erbB-2 may be involved in astrocytic brain tumours. We screened immunohistochemically c-erbB2 protein (p185) expression in 94 astrocytic grade 1-4 neoplasms of the brain. The amplification of the c-erbB-2 oncogene was investigated in protein overexpression cases by dual colour fluorescence in situ hybridisation (FISH). p185 overexpression was correlated with p53 and epidermal growth factor receptor (EGFR) expression, as well as with clinicopathological features. Only two anaplastic (grade 3) astrocytomas and one glioblastoma (grade 4) showed overexpression of p185 protein by immunohistochemistry (monoclonal MAb1 antibody TA250), whereas none of the grade 1-2 astrocytomas was positive. Interestingly, the expression of p185 was confined solely to the cytoplasm of neoplastic astrocytic cells and not to the cell membranes as found in malignancies with amplification of the c-erbB-2 oncogene. Two of the three overexpression cases were also positive by EGFR. No amplification of the c-erbB-2 gene was observed by FISH in the three tumours with immunohistochemical p185 overexpression or seven weakly positive/negative tumours. In conclusion, our results suggest that p185 overexpression is infrequent in astrocytomas, that it is of no important diagnostic or prognostic value and that c-erbB-2 oncogene amplification is not seen in the few cases in which there is overexpression.
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PMID:c-erbB-2 in astrocytomas: infrequent overexpression by immunohistochemistry and absence of gene amplification by fluorescence in situ hybridization. 860 96

The HER-2/neu gene product, p185(neu), is a membrane-bound receptor with tyrosine kinase activity. High levels of p185(neu) is correlated with intrinsic chemoresistance of non-small cell lung cancer (NSCLC) cell lines. We investigated the effects of tyrphostin AG825, a selective tyrosine kinase inhibitor preferentially inhibiting HER-2/neu kinase, on the chemosensitivities and on the drug-induced cell cycle changes of NSCLC cell lines that expressed different levels of p185(neu). Compared to the low-p185(neu) expressing cell lines, we found that the high-p185(neu) expressing cell lines were more resistant to doxorubicin, etoposide, and cis-diamminedichloroplatinum(II) but more sensitive to AG825. AG825 was able to significantly enhance the chemosensitivities of the high-p185(neu) expressing cell lines, whereas it had little effect on the chemosensitivities of the low-p185(neu) expressing cells, with a few exceptions in which minor antagonistic effects were observed. Although high concentrations of AG825 could reduce the drug-induced G(2) arrest that was accompanied by the activation of phosphorylated p34(cdc2), we failed to find any remarkably differential effects of AG825 on drug-induced G(2), arrest and the accompanying phosphorylation status of p34(cdc2) of the high- and and the low-p185(neu) expressing cell lines. In summary, tyrphostin AG825 can enhance chemosensitivity in high- but not in low-p185(neu) expressing NSCLC cell lines. This differential effect cannot be explained by the alterations of drug-induced cell cycle changes by AG825. Our results provide a rationale to develop p185(neu)- specific tyrphostin and to test them in combination with anticancer agents in vivo and in clinical trials.
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PMID:Enhancement of chemosensitivity by tyrphostin AG825 in high-p185(neu) expressing non-small cell lung cancer cells. 864 Jul 63

The HER2/neu protooncogene encodes a transmembrane receptor tyrosine kinase of Mr185 kDa (called p185) which is structurally and functionally homologous to the epidermal growth factor receptor. Shc proteins are important downstream signal transducers of receptor tyrosine kinases. We reported here a novel finding that p66Sch was absent or nearly absent in p185-overexpressing breast cancer cells. This inverse correlation of p185 overexpression and p66Shc expression is probably specific to breast cancer cells because this phenomenon was not observed in p185-overexpressing human ovarian, lung, or oral cancer cells, or mouse fibroblast cells. In contrast, the p52Shc and p46Shc isoforms were expressed at similar levels in both p185-overexpressing and p185 basal level breast cancer cell lines. Furthermore, tyrosine phosphorylation of p52Shc and p46Shc and subsequent formation of Shc/Grb2 complex were detected in breast cancer cells in which the p185 tyrosine kinase is activated, indicating that p66Shc is not required for mediating the HER-2/neu signaling pathway in breast cancer cells.
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PMID:p66Shc isoform down-regulated and not required for HER-2/neu signaling pathway in human breast cancer cell lines with HER-2/neu overexpression. 866 Mar 24

The role of oncogenes in carcinoma of unknown primary site (CUP) has not yet been elucidated. In the present study the expression of the c-myc p62, ras p21 and c-erB-2 p185 oncoproteins were studied by a 3-step immunoperoxidase technique in 26 cases of CUP. Positive immunoreactivity was observed in 96% of the cases for c-myc, 92% for ras and in 65% for c-erb-2, with at least half of tumor cells labelled in 85%, 92% and 58% respectively. The degree of staining intensity was considered moderate or strong in more than half of the cases for all oncogene products. In conclusion, our results showed that patients with CUP have an extremely high overexpression of all three oncogenes studied. Nevertheless, the biological role of these overexpressed oncoproteins, their relationship with different histological or clinical parameters and their diagnostic or prognostic value need further evaluation.
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PMID:Overexpression of C-myc, Ras and C-erbB-2 oncoproteins in carcinoma of unknown primary origin. 866 24

The HER-2/neu gene is frequently amplified and/or its protein product, p185, is overexpressed in a number of human cancers. Overexpression of p185 correlates with poor prognosis and low survival rates in ovarian cancer patients. We previously found that the K1 mutant of SV40 large T antigen inhibits rat neu promoter and suppresses mutation-activated rat neu transformation in mouse fibroblasts. We show here that K1 also inhibits human HER-2/neu promoter in human ovarian cancer cells. To investigate whether K1 can suppress HER-2/neu transformation and thus is a potential therapeutic agent, we used an orthotopic ovarian cancer model in which mice were injected intraperitoneally with HER-2/neu-overexpressing human ovarian cancer cells to induce tumor development. The tumor-bearing mice were then treated with K1-liposome complex weekly. We found that liposome-mediated K1 gene transfer decreased the p185 protein level by K1 expression in these cancer cells and significantly prolonged mice survival; about 40% of these treated mice were alive for more than 1 year without any tumor development. On the other hand, the animals from control groups that did not receive this gene therapy all developed tumors and died within 7 months. The results indicate that liposome-mediated K1 gene transfer is able to suppress tumor development from HER-2/neu-overexpressing ovarian cancer cells in mice.
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PMID:Mutant SV40 large T antigen as a therapeutic agent for HER-2/neu-overexpressing ovarian cancer. 872 81

The erbB-2 proto-oncogene encodes a transmembrane protein (p185) that is a tyrosine kinase sharing high homology with the epidermal growth factor receptor. Its expression in mammary cell lines is modulated by estrogens, epidermal growth factor, and several other factors at the RNA and/or protein levels. We have used in situ hybridization, immunoblot, and immunohistochemistry to study the expression of erbB-2 in the rat mammary gland at various stages of differentiation. erbB-2 RNA is present at low levels in mammary glands from virgin, mid-pregnant, and lactating female rats. Increased RNA levels can be detected in early and late pregnancy. In all samples, erbB-2 RNA has been found in all epithelial cells. Immunohistochemistry with antisera directed against the intracellular domain of p185 has shown that only a minority of cells are stained in virgin and early pregnant samples, whereas no staining is seen in late pregnant and lactating mammary glands. In contrast, immunoblot analysis has detected the highest levels of p185 in late pregnancy and during lactation. This may reflect either that the cellular content of p185 is too low to be detected by immunohistochemistry, or that the epitopes are not accessible to the antisera in situ. Taken together, our data indicate that erbB-2 is expressed by mammary epithelial cells at all physiological stages and suggest that erbB-2 expression is modulated at both the RNA and protein level in vivo.
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PMID:Expression of the erbB-2 proto-oncogene during differentiation of the mammary gland in the rat. 877 54

It has been reported that breast tumors that overexpress c-erbB-2/neu are less responsive to certain adjuvant chemotherapy regimens than those that express a normal amount of the gene product. To investigate whether overexpression of the c-erbB-2/neu-encoded p185 can indeed lead to increased chemoresistance in breast cancers, we introduced the human c-erbB-2/neu gene into the very low p185-expressing MDA-MB435 human breast cancer cells and examined Taxol sensitivities among the parental MDA-MB-435 cells and stable transfectants which express increased levels of p185. The p185-overexpressing MDA-MB-435 transfectants were more resistant to Taxol than the parental cells. The increased Taxol resistance was not accompanied by changes in doubling time and S-phase fraction. The increased Taxol resistance was independent from oncogenic transformation since it was observed only in c-erbB-2/neu-transformed cells and not ras-transformed cells when oncogene-transformed NIH3T3 cells were examined. To study whether p185 induced Taxol resistance through the mdr-1 pathway, we examined the mdr-l-encoded p170 levels in these transfectants. The MDA-MB-435 cells expressed very low levels of p170 and there was no increase of p170 expression in the p185-overexpressing MDA-MB-435 transfectants. Furthermore, these transfectants were not sensitized to Taxol treatment by mdr-1 blocker thioradazine. These data demonstrated that overexpression of c-erbB-2/neu can lead to intrinsic Taxol resistance independent from mdr-1 mechanisms.
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PMID:Overexpression of c-erbB-2/neu in breast cancer cells confers increased resistance to Taxol via mdr-1-independent mechanisms. 880 11

Monoclonal antibodies targeting c-erbB-2 protooncogene product p185 were conjugated with adriamycin via a pH-sensitive spacer. The resultant antibody-adriamycin conjugates showed immunoselective binding, internalization and cytotoxicity to p185-positive human breast cancer cell SKBr-3 and gastric cancer cell MKN-7, but not to normal human lymphocytes.
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PMID:Immunoselective cell growth inhibition by antibody-adriamycin conjugates targeting c-erbB-2 product on human cancer cells. 884 23

The relationship between expression of the c-erbB-2 proto-oncogene and the biology of breast cancer has been investigated widely, most studies using immunohistochemistry in formalin-fixed, paraffin-embedded tissues. This technique is at best semiquantitative and there is a high degree of interstudy variability because of its subjective nature and poor methodological standardization. The relationship between the levels of expression and biology can be examined thoroughly only with an accurately quantitative technique. We have developed a radioimmunohistochemical assay to measure p185(erbB-2) in tissue biopsy specimens. The method involves incubating frozen sections with 125I-labeled monoclonal antibody, microautoradiograpy, and grain counting with image analysis. Sections of cell pellets with known c-erbB-2 levels are processed with each batch of samples as internal calibration standards. We have quantified c-erbB-2 expression in 60 breast carcinomas and compared the results with conventional immunohistochemistry. Radioimmunohistochemistry measured receptor levels throughout the range of expression in breast carcinomas, whereas conventional immunohistochemistry detected the protein only in the highest expressing tumors. The quantitative, objective data produced by radioimmunohistochemistry allow a more thorough evaluation of the relationship between c-erbB-2 expression and tumor biology. This technique may have applications in other fields where quantitative data is required and relevant monoclonal antibodies are available.
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PMID:Quantitative radioimmunohistochemical measurements of p185(erbB-2) in frozen tissue sections. 891


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