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)

Two cell lines (University of Michigan squamous carcinoma of the vulva UM-SCV-1A and UM-SCV-1B) were established from the primary tumor and a malignant pleural effusion of a 62-year-old woman. Both tumor specimens grew vigorously in vitro and could be passaged after only 14 and 10 days in culture, respectively. Both cell lines undergo 3 population doublings in 4 days, reaching saturation densities of 5 x 10(5) cells/cm2, and have been carried through more than 30 in vitro passages. In nude mice the cultured cells initially formed tumors but these regressed 2-3 weeks after inoculation. The regressing mouse tumors consisted of poorly differentiated squamous carcinoma surrounded by an inflammatory lymphoid infiltrate. The UM-SCV-1 cell lines express membrane antigens typically displayed by squamous-cell carcinomas. These include the HLA class-1 light chain beta 2-microglobulin, pemphigus, pemphigoid, and the alpha 6 beta 4 integrin defined by the UM-A9 monoclonal antibody (MAb). In contrast to the A431 vulvar carcinoma, these tumor lines do not have amplified expression of the epidermal growth factor (EGF) receptor. Although tissue from the primary tumor contained low levels of estrogen receptor activity, no receptor activity was detected in the cell lines. Nevertheless, both lines were sensitive to growth inhibition by tamoxifen. This effect was not reversible by estradiol, indicating an estrogen-receptor-independent mechanism. The tumors were both hypotetraploid, contained the same chromosome rearrangements and had stable karyotypes in vitro. Each contained inv(1)(p36.3q32.1), del(4)(q12), dic(4;11)(q12;p11.2), i(5p), der(6)t(3;6)(q25.1;p21.1), several rearrangements involving chromosomes 8 and 14, + i(13), i(18p), a dicentric t(11;19), and 2 or 3 unidentified markers. Since the karyotypes of both tumors were the same, no major karyotypic change was associated with metastatic spread. These paired primary and metastatic SCC lines from an unusually aggressive vulvar carcinoma provide an in vitro model for analysis of the biological basis of this tumor's behavior.
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PMID:Phenotypic characterization, karyotype analysis and in vitro tamoxifen sensitivity of new ER-negative vulvar carcinoma cell lines, UM-SCV-1A and UM-SCV-1B. 233 95

Membrane protein levels of erbB-2 and epidermal growth factor (EGF) receptor as well as gene aberrations affecting these proto-oncogenes in human mammary cancer were determined in primary and metastatic lesions. Among 57 patients erbB-2 gene amplification was detected in 11 tumors (19%). In 10 of these patients where expression levels could be assayed gene amplification was associated with a high level of erbB-2 protein. In contrast, EGF receptor gene amplification with over-expression of the protein product was observed in 2 tumors (4%). In addition, 14 out of 53 (26%) primary tumors exhibited moderately increased erbB-2 protein levels in the absence of gene amplification. Similar aberrations resulting in overexpression of EGF receptor protein without detectable gene amplification were associated with 2 tumors (4%) among 47 patients analyzed. In 7 patients, expression level and gene copy numbers of erbB-2 or EGF receptor were similarly altered in the primary tumor and metastatic lesions derived from the same patient. Concordance of increased receptor gene expression in primary and metastatic lesions combined with the observation that such alterations are detectable as early as stage I and II mammary tumors, suggests that overexpression of erbB protooncogene family members can develop early in breast cancer and is maintained during tumor progression. Comparison of erbB-2 overexpression with clinical disease parameters revealed a correlation of this alteration with inflammatory mammary carcinoma (P = 0.042) implying an association of elevated erbB-2 protein levels with enhanced malignancy of the tumor cell in vivo.
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PMID:Overexpression of erbB-2 or EGF receptor proteins present in early stage mammary carcinoma is detected simultaneously in matched primary tumors and regional metastases. 256 57

Short-term cultures of normal human mammary epithelial cells were used to determine the extent to which c-myc, c-Ha-ras1, and c-erbB-2 proto-oncogenes were expressed in proliferating normal cells. This level of expression was compared with that of primary tumor cells, malignant effusion cells, or permanently established breast cancer cell lines. Pure preparations of epithelial organoids from seven different reduction mammoplasty tissue samples yielded proliferating normal epithelial cells upon short-term tissue culture. In every sample, proto-oncogene transcript levels increased upon short-term culture of the epithelial cells. These levels often exceeded by 10-fold the levels measured in uncultured organoids from the same tissue. In four of the seven cultured normal breast samples, at least one of the proto-oncogenes increased its expression to a level equaling or exceeding that found in a proliferating breast cancer cell line, MCF7. One effusion metastasis sample and two primary ductal adenocarcinomas were also examined for proto-oncogene expression. The effusion metastasis sample expressed high levels of c-erbB-2 messenger RNA, in accord with its amplified gene copy number; otherwise, the levels of proto-oncogene transcripts were low in unprocessed tumor and uncultured organoids, but they increased with proliferation of the tumor cells in culture. These results indicate that the variable expression of these proto-oncogenes observed in breast biopsy specimens needs to be controlled for cellular growth rate or proliferation index. Furthermore, these findings suggest that dysregulated proto-oncogene expression, rather than overexpression per se, needs to be evaluated as a possible mechanism contributing to the development of human breast cancer.
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PMID:Expression of c-myc, c-Ha-ras1, and c-erbB-2 proto-oncogenes in normal and malignant human breast epithelial cells. 257 2

This study was carried out on 222 samples from 37 gastric carcinomas to assess the incidence of multiple stem lines in primary tumors and metastasis as reflected by multiple DNA stem lines and their relationship to epidermal growth factor (EGF) receptor expression, histologic grade, tumor size, and degree of wall infiltration. Fifteen primary tumors (40.5%) were homogeneously diploid/peridiploid whereas 22 (59.5%) were aneuploid. In the lymph node metastasis, seven patients (29.2%) had an homogeneous diploid/peridiploid pattern in all metastatic lymph nodes. On the other hand, 17 (70.8%) had at least one aneuploid peak in the lymph node metastasis. DNA content heterogeneity was seen in 12 (33%) of primary tumors whereas 14 (66.6%) of 21 patients had multiple cell clones in the metastasis. Therefore, 12 patients had a metastatic clone which was not observed in the primary tumor. DNA content heterogeneity was seen even in tumors with submucosal invasion suggesting that this phenomenon is also present at earlier stages. No correlation between the histologic grade and the DNA distribution was observed. Furthermore, histologic heterogeneity was independent of DNA content heterogeneity. The EGF receptor expression was observed in six of the 23 patients in whom this analysis was done. The EGF receptor expression was constant in all samples which were studied and even samples with a different DNA content and histologic grade were stables for the EGF receptor expression.
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PMID:Gastric cancer heterogeneity. 291 85

Overexpression and amplification of the erbB-2 (neu) is thought to play a major role in mammary cancer. Although studies suggest that Neu is directly involved in the genesis of mammary tumors, the molecular mechanism by which Neu induces tumors is not well understood. Recently, we have demonstrated that the activity of c-Src tyrosine kinase is elevated in Neu-induced mammary tumors and this elevated activity correlates with its capacity to physically associate with Neu. To explore whether other members of the c-Src family are activated in these mammary tumors, we measured the in vitro kinase activity of the c-Yes and Fyn kinases in protein extracts derived from mammary tumor tissue and morphological normal adjacent tissue. These analyses revealed that c-Yes kinase activity was elevated in Neu-induced tumors by comparison to the adjacent tissue. By contrast, no significant activation of the Fyn kinase was noted in these tumors. Activation of c-Yes tyrosine kinase correlated with the capacity of c-Yes to associate with Neu in vivo in lysates derived from primary tumor samples. Studies with Rat.2 fibroblasts overexpressing activated Neu revealed that c-Src requires the presence of tyrosine phosphorylated Neu for its ability to interact with Neu in vivo. Moreover, analyses using radiolabeled c-Yes SH2 fusion protein revealed that this interaction is likely occurring in a direct fashion. Although both c-Src and c-Yes kinase associate with Neu in vivo, a tyrosine phosphorylated protein of 89 kd (p89) was found associated with c-Src but not with c-Yes in cell lysates derived from mammary epithelial cells transformed by either Neu or PyV middle T antigen. Furthermore, this tyrosine phosphorylated protein was not detected in c-Src complexes derived from fibroblasts transformed by either Neu or PyV middle T. These observations suggest that p89 associates with c-Src only in mammary epithelial cells and not in fibroblasts.
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PMID:Activation of Src family kinases in Neu-induced mammary tumors correlates with their association with distinct sets of tyrosine phosphorylated proteins in vivo. 747 8

In search of biomarkers that predict of human prostate cancer progression, we hypothesized that these markers must be expressed in prostatic epithelial cells during multi-step prostate carcinogenesis. Since both genetic and epigenetic factors have been implicated in human prostate cancer development, two osseous-metastatic experimental models were developed in our laboratory, one based on gene transfection and the other on stromal-epithelial interaction studies. In the genetic model, PC-3 cells transfected with point-mutated c-erbB-2/neu oncogene subsequently acquired the potential to metastasize from the prostate to soft tissues and the skeleton. In the epigenetic model, sublines derived from the parental androgen-dependent LNCaP cell line metastasized from the primary tumor to the lymph node and bone. Cells with known lineage relationships were cloned from both the primary and the metastatic tumors and were characterized extensively using cellular, biochemical, immunohistochemical, and molecular techniques. Relevant stage-specific biomarkers associated with prostate cancer progression in these two models were defined and used to evaluate human prostate tissues obtained from the clinic. In this communication, we focused our discussion on the potential importance of c-erbB-2/neu oncogene, vimentin, hepatocyte growth factor/scatter factor and its receptor, c-met oncogene, tumor angiogenesis and neuroendocrine factors as biomarkers for human prostate cancer progression.
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PMID:Biomarkers associated with prostate cancer progression. 752 53

The issue of whether multifocal breast cancer represents intramammary spread from a single primary tumor or multiple synchronous tumors remains unresolved. We have used a series of immunocytochemical markers, B72.3, DF3, c-erbB-2, SP-1, CEA, and p53, to attempt to answer this question. Of 24 cases with separate discrete synchronous tumors in the same breast, 10 were histologically and immunocytochemically identical, five were histologically similar but immunocytochemically different, two were histologically different but immunocytochemically identical, and in seven cases the tumors were different both histologically and immunocytochemically. In seven of the 24 cases lymph nodes containing metastatic tumor were also available; in each instance, the immunoreactivity of the metastasis was similar to one or other of the tumors in the breast. This study indicates that multifocal breast cancer may result from either intramammary spread from a single primary tumor or multiple synchronous primary tumors.
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PMID:Mechanisms of multifocal breast cancer: an immunocytochemical study. 767 96

Two new human mammary carcinoma lines originating from surgical material were established in nude mice. According to the adopted criteria, the tumor 4049 has been classified as estradiol receptor positive and mammary carcinoma 4296 as estradiol receptor negative. Both tumors proved to be c-erbB-2 protein positive and EGF-receptor negative. In contrast to carcinoma 4296, the in vitro growth and the take rate of mammary carcinoma 4049 in nude mice seems to be dependent on stromal components. Pretreatment of mice with estradiol/peanut oil before tumor engraftment was an essential precondition for the growth of the primary tumor in nude mice. After successful establishment the tumor growth was significantly stimulated by estradiol. The growth rate of mammary carcinoma 4296 was independent of any supplementation of estradiol. The two breast tumors were characterized with regard to their growth behaviour, histology, and sensitivity to cytostatics and antihormones. They are considered suitable tumor models for the testing of antineoplastic substances and for biological experiments.
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PMID:Establishment and characteristics of two new human mammary carcinoma lines in nude mice with special reference to the estradiol receptor status and the importance of stroma for in vivo and in vitro growth. 786 48

The introduction of c-erbB-2 protein to clinical medicine as a prognostic indicator and tumor marker is desired. The authors determined the concentration of c-erbB-2 protein in 81 breast cancer tissues by enzyme immunoassay. The concentration of c-erbB-2 protein in breast cancer tissues showed a broad spectrum. A significant correlation was observed between tissue c-erbB-2 protein concentration and estrogen receptor status or immunohistochemical determination. In patients with distant metastases, there was a close association between c-erbB-2 protein concentration in the primary tumor and serum c-erbB-2 protein level. Cases with a high tumor concentration of c-erbB-2 protein (> 1000 U/mg total protein; 18.5% of cases) had a poor prognosis. From the above, we concluded the measurement of tissue c-erbB-2 protein by enzyme immunoassay to be clinically useful in breast cancer.
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PMID:Quantitative analysis of c-erbB-2 protein in breast cancer tissue by enzyme immunoassay. 790 94

Concentrations of a fragment of the c-erbB-2 translational product (p185 fragment) were measured in serum of 70 breast cancer patients, 19 healthy blood donors, and 18 pregnant women using a heterogenic enzyme immunoassay. The serum concentrations of blood donors and pregnant women were below 30 kU/l. Breast cancer patients showed serum concentrations up to 578 kU/l. All 9/70 patients with serum concentrations higher than 30 kU/l had clinical evidence of metastatic disease and the serum levels of all 35/70 patients without metastasis lay within the normal range. From 9/37 patients with p185 overexpression of the primary tumor in immunohistochemical analysis 3/9 patients with metastatic disease had elevated serum levels higher than 30 kU/l. In all, 6/9 patients without metastasis serum levels were below 30 kU/l. The data of the present study suggest that determination of serum p185 fragment concentrations may be useful as a diagnostic tool in postoperative follow-up of breast cancer patients with c-erbB-2 overexpression of the primary tumor.
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PMID:Determination of a fragment of the c-erbB-2 translational product p185 in serum of breast cancer patients. 809 50


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