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)

Using a commercial kit with antibodies against the ectodomain of c-erbB-2 protein, we detected c-erbB-2 immunoreactivity in human serum. We found that the percentages of patients with elevated serum c-erbB-2 immunoreactivities were 35, 21, and 9% in breast, prostate, and ovarian carcinoma, respectively. The majority of the elevated immunoreactivities were associated with sera containing highly elevated tumor markers with the highest in breast carcinoma (35%) and lowest in ovarian cancer (9%). Excellent correlations were also observed between the serum levels of c-erbB-2 immunoreactivity and the dominant tumor markers in serial specimens from individual cancer patients. We could also detect the c-erbB-2 immunoreactivity in the cytosols prepared from the breast tumor tissue for estrogen and progesterone receptor (ER & PgR) measurements using the same commercial kit for serum studies, and the intact c-erbB-2 oncoprotein (p185) in the extracts of the tissue membrane fractions with a different kit designed for tissue extract. The level of c-erbB-2 immunoreactivity in the cytosol from 124 human breast tumor specimens had an excellent correlation with the cell membrane concentrations of p185 (gamma = 0.89). Most of the elevated cytosol c-erbB-2 immunoreactivities were also found to associate with breast tumor specimens containing low concentrations of ER & PgR. It appears that measuring the c-erbB-2 immunoreactivity potentially could be used as a prognostic marker without performing tissue biopsies and also as a serum tumor marker for managing cancer patients.
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PMID:Measurement of c-erbB-2 proteins in sera from patients with carcinomas and in breast tumor tissue cytosols: correlation with serum tumor markers and membrane-bound oncoprotein. 754 55

Overexpression of the c-erbB-2 proto-oncogene product (p185c-erbB-2) occurs frequently in different types of human cancer and is correlated with a significantly decreased survival in ovarian cancer patients. The effect of c-erbB-2 anti-sense phosphorothioate oligodeoxynucleotides (S-ODNs) was examined on the ovarian cancer cell line SK-OV-3. p185c-erbB-2 levels were specifically reduced by a single-dose application of 5 microM c-erbB-2 anti-sense S-ODNs. This was accompanied by a 60% inhibition of anchorage-dependent cell growth. More strikingly, c-erbB-2 anti-sense S-ODNs almost completely abrogated serum-induced cell spreading. A control of complementary sense oligodeoxynucleotides did not show significant inhibitory effects on cell growth or on cell spreading. The inhibition of cell spreading was imitated by a monoclonal antibody (9G6) targeting the extracellular domain of p185c-erbB-2 and by the tyrosine kinase inhibitor erbstatin. The inhibitory activity of these 2 compounds was lost after a few hours, while the inhibition of serum-induced cell spreading by anti-sense S-ODNs was still present after 24 hr. Our results show that c-erbB-2 anti-sense S-ODNs effectively inhibit the mitogenic and spreading activity of p185c-erbB-2 in ovarian cancer cells. Thus, anti-sense strategies have the potential of providing new strategies for the therapy of ovarian cancer.
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PMID:c-erbB-2 anti-sense phosphorothioate oligodeoxynucleotides inhibit growth and serum-induced cell spreading of P185c-erbB-2-overexpressing ovarian carcinoma cells. 759 Dec 73

We have determined the average gene copy numbers (AGCN) of the erbB-1 gene, encoding the epidermal growth factor receptor (EGF-R), the erbB-2 and the erbB-3 genes in breast, ovarian, oral, and lung cancer tissue by using double-differential PCR (ddPCR). The ddPCR method comprises the co-amplification of the single-copy gene HBB, the erbB-1, erbB-2 and erbB-3 oncogenes and the second single-copy reference gene SOD2 under equal reaction conditions. In a retrospective study the AGCN of the erbB genes and the time up to the appearance of metastases were subjected to life-table analysis in 128 women with primary breast cancer. Patients whose breast cancer tissue showed an AGCN for erbB-1 of less than 0.4 and greater then 1.6, as expected from the literature, for erbB-2 of greater than 2.0 and for erbB-3 of less than 1.75 had decreased disease-free survival (DFS). The quotient of erbB-1 and erbB-2 AGCN was the most significant in multivariate Cox analysis followed by nodal status and progesterone receptor status. In extensive studies a similar association between erbB AGCN and metastasis was seen in ovarian cancer and oral cancer, though erbB oncogene aberrations in those entities were not as frequent as in breast cancer. The AGCN of erbB oncogenes may not be of prognostic value in untreated lung cancer patients.
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PMID:Prognostic relevance of aberrations in the erbB oncogenes from breast, ovarian, oral and lung cancers: double-differential polymerase chain reaction (ddPCR) for clinical diagnosis. 760 71

Epithelial ovarian cancer probably occurs due to activation of several different combinations of genes, which produce cancers that vary biologically and clinically. We tested this hypothesis in 100 consecutive ovarian carcinomas by molecular biology techniques at the DNA and protein levels in three genes (erbB-2, myc, ras), which are frequently altered in this tumor system. Abnormally high expression of erbB-2 gene encoded p185 protein was observed in 31% of the samples, while erbB-2 gene amplification was detected by Southern analysis in 8%. ErbB-2 abnormal gene expression did not significantly affect the clinical outcome of patients, conferring a marginal worsening of survival. In 25 out of 96 (26%) tumor samples there was myc amplification. Higher levels of the ras-encoded p21 protein than in normal ovaries and benign ovarian tumors were found in 45% of the samples. Simultaneous overexpression of p185 and p21 was associated with shorter disease free (p = 0.02) and overall survival (p = 0.04) at significance levels notably higher than those observed for these oncoproteins singly. In addition, survival of patients with myc amplification and high p185/p21 coexpression was significantly worse (p < 0.05) than that of patients with normal levels. Our data suggest that concurrent abnormal gene expression may act synergistically to endow ovarian tumor cells with a highly aggressive phenotype. Evaluation of these genes may be helpful in the biological characterization of ovarian cancer and in defining individual patient prognosis.
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PMID:Concurrent abnormal expression of erbB-2, myc and ras genes is associated with poor outcome of ovarian cancer patients. 765 38

Overexpression of HER-2/neu has been demonstrated in human ovarian cancer and correlated with poor prognosis. We previously found that the adenovirus type 5 early region 1A (E1A) gene product can repress overexpression and suppress the tumorigenic potential of the HER-2/neu-overexpressing cancer cells. To develop an efficient HER-2/neu-targeting gene therapy with E1A, a replication-deficient adenovirus containing the E1A gene, Ad.E1A(+), was used to transduce the HER-2/neu-overexpressing human ovarian cancer cell line SK-OV3.ip1. Tumor cell growth in vitro and colony formation in soft agarose were greatly inhibited by Ad.E1A(+) transduction. To test therapeutic efficacy in vivo, tumor-bearing mice were established by i.p. injection with ovarian cancer cells and treated by i.p. injection of 10(8) PFU viral solution containing either replication-deficient Ad.E1A(+); control virus Ad.E1A(-) which is the same adenovirus as Ad.E1A(+) except for E1A deletion, or just PBS. Ad.E1A(+) significantly prolonged survival in treated mice for 1 year (80%) whereas in control groups, all mice died of cancer within 4.5 months. Immunohistochemistry analysis indicated that Ad.E1A protein was expressed in tumor tissue and expression of HER-2/neu p185 protein was suppressed in vivo. As a control, another ovarian cancer cell line 2774, in which HER-2/neu is expressed at a basal level, was also inoculated i.p. following the same therapeutic procedure. Ad.E1A(+) could not prolong survival of 2774 cells, indicating that Ad.E1A(+) specifically targeted HER-2/neu-overexpressing tumor cells and functioned as an antitumor agent.
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PMID:HER-2/neu-targeting cancer therapy via adenovirus-mediated E1A delivery in an animal model. 776 Oct 95

The proto-oncogene HER2/neu encodes for a 185 kDa transmembrane protein with extensive homology to the epidermal growth factor (EGF) receptor. We have previously shown a correlation between HER2/neu expression and the level of in vitro cytotoxicity of tumour-associated lymphocytes (TAL) versus autologous tumour. In addition, we have recently demonstrated that tumour-associated cytotoxic T-lymphocytes (CTL) from ovarian and breast cancer patients can recognize a HER2/neu derived peptide epitope when presented in the context of HLA-A2. Since repeated tumour stimulation of CTL enhances both proliferation and cytotoxicity against autologous tumour, we hypothesized that repeated peptide antigen stimulation would have a similar effect. To be therapeutically useful, the peptide antigen must meet the following conditions: (1) the peptide must be immunogenic and cause a proliferation of CTL to adequate therapeutic numbers, and (2) the peptide-specific CTL which are generated must be cytotoxic against autologous tumour. To test our hypothesis, T-lymphocytes isolated from the ascites of four consecutive HER2/neu+ ovarian cancer patients were initially stimulated with solid phase anti-CD3 antibody and divided into three groups: (1) treatment with recombinant interleukin-2 (IL-2) alone, (2) IL-2 plus weekly stimulation with irradiated autologous tumour cells, and (3) IL-2 plus weekly stimulation with a HER2/neu derived peptide. Peptide-stimulated and tumour-stimulated CTL showed similar increases in proliferation with both groups consistently reaching therapeutic numbers. Peptide-stimulated CTL demonstrated significantly enhanced cytotoxicity against autologous tumour in 4-h chromium release assays as compared to the IL-2 alone group.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:In vitro stimulation of ovarian tumour-associated lymphocytes with a peptide derived from HER2/neu induces cytotoxicity against autologous tumour. 778 Jun 12

C-erbB-2(HER-2/neu) proto-oncogene is mainly expressed in epithelial tissue and activated due to its amplification. Amplification of the C-erbB-2 proto-oncogene has been associated with poor prognosis in human ovarian cancer. Our study was to examine whether amplification is more frequently observed in ovarian cancer, or it is associated with poor prognosis of human ovarian cancer in China. The DNA of ovarian cancers was extracted and consequently digested with restriction endonuclease EcoRI, electrophoresed in 0.8% agarose gels and blotted onto nitrocellulose filter with Southern transferring method. It was then hybridized with a 32P-labelled C-erbB-2 probe and subsequently underwent autoradiography. The result has shown that the C-erbB-2(HER-2/neu) gene was amplified in 8 of 26 human ovarian cancers (30.8%). The clinical data showed that all of the 8 cases with the amplified C-erbB-2 were in their advanced stage (III-IV). Five of the patients died from 2 to 4 months after operation. These data suggest that amplification of the C-erbB-2 gene may play a role in the pathogenesis of ovarian carcinoma; it is frequently observed in advanced ovarian cancer and is associated with poor prognosis for these patients.
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PMID:Amplification of the C-erbB-2(HER-2/neu) proto-oncogene in ovarian carcinomas. 780 42

An epithelial ovarian cancer cell line is established from a patient with recurrent familial ovarian cancer. Two of the patient's sisters and her mother have also had ovarian cancer. The histological resemblance of the cell line to the patient's Stage IV, Grade 3 papillary serous ovarian primary cancer is striking. The cell line does not secrete CA125 and is estrogen and progesterone receptor negative. Overexpression of the p53 tumor suppressor gene but not the HER-2/neu oncogene was detected by immunohistochemical analysis. An unusual chemosensitivity to cisplatin, doxorubicin, etoposide, and taxol is demonstrated, suggesting that a chemosensitivity mechanism might explain prolonged survival of some patients with familial ovarian cancers. This truly unique cell line should prove invaluable in the further evaluation of molecular genetic changes associated with familial ovarian cancers.
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PMID:Isolation and preliminary characterization of an ovarian carcinoma cell line from a patient with familial ovarian cancer. 782 46

Overexpression of HER-2/neu, a 185-kDa tyrosine kinase growth factor receptor, in human ovarian cancers has been correlated with a poor prognosis for survival of the disease. Previous studies have demonstrated that dexamethasone (Dex) induces a dose-dependent increase in HER-2/neu mRNA levels in the ovarian cancer cell line SK-OV-3 by stabilizing the HER-2/neu message. We extended these studies to test whether estrogen (Es), progesterone (Pr), and Dex were capable of regulating HER-2/neu mRNA levels in the human ovarian cancer cell lines NIH:OVCAR-3, SW 626, OVCA 433, and Caov-3. Southern blotting demonstrated that all four cell lines contained a single copy of the 12.5-kb HER-2/neu gene. Blotting techniques demonstrated low to barely detectable levels of HER-2/neu mRNA and protein in these cell lines. To determine whether steroids regulated HER-2/neu expression, all four ovarian cancer cell lines were cultured in the presence of 1 x 10(-7) M Es, Pr, or Dex and Northern blotting was completed. Unlike SK-OV-3 cells, the cell lines tested did not respond to the steroid treatments with alterations in their HER-2/neu mRNA levels. In conclusion, neither Es, Pr, nor Dex regulates HER-2/neu mRNA levels in NIH:OVCAR-3, SW 626, OVCA 433, and Caov-3 ovarian cancer cells. Future therapeutic manipulations of HER-2/neu should not involve hormonal intervention.
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PMID:Steroid hormonal independence of HER-2/neu mRNA expression in four human ovarian carcinoma cell lines. 783 82

C-erbB-2 (HER-2/neu) proto-oncogene is mainly expressed in epithelial tissue and activated due to its amplification. Amplification of the C-erbB-2 proto-oncogene is associated with poor prognosis in human ovarian cancer. We examined whether amplification of C-erbB-2 is common in ovarian carcinoma or is associated with poor prognosis. The DNA of ovarian carcinoma was extracted and consequently digested with restriction endonuclease EcoRI, electrophoresed in 0.8% agarose gels and blotted onto nitrocellulose filter with Southern transfering method. It was hybridized with a 32p-labelled C-erbB-2 probe and subsequently underwent autoradiography. It was shown that the C-erbB-2 (HER-2/neu) gene was amplified in 8 of 26 human ovarian carcinomas (30.8%). Clinically the 8 patients with the amplified C-erbB-2 were in their advanced stage (III-IV). Five of the patients died from 2 to 4 months after operation. These findings suggest that amplification of the C-erbB-2 gene may play a role in the pathogenesis of ovarian carcinoma, it is frequently observed in advanced ovarian carcinoma and associated with poor prognosis for these patients.
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PMID:[The relation between prognosis and amplification of the c-erB-2 (HER-2/neu) proto-oncogene in ovarian carcinomas]. 786 5


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