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)

The NEU proto-oncogene encodes a 185,000 dalton transmembrane glycoprotein with extensive homology to epidermal growth factor receptor. In the current study the effect of exogenous NEU expression on phenotype and growth properties of cells established lines was examined. The replication defective retroviruses were used to express constitutively NEU cDNA in the Rat-1, NIH3T3 and Balb/c3T3 cells. In spite of the practically similar NEU mRNA and protein content in infected cells only in Balb/c3T3 cells, high NEU expression ultimately led to oncogenic transformation. The Rat-1 cells were practically insensitive to oncogenic action of NEU. Subpopulation divergency with respect to NEU-dependent transformation was also revealed in infected NIH3T3 cells. These results suggest the existence of unknown host-specific factor(s) determining the response of cells to NEU overexpression.
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PMID:Polymorphic changes of cell phenotype caused by elevated expression of an exogenous NEU proto-oncogene. 196 37

The Drosophila epidermal growth factor receptor homolog (DER) displays sequence similarity to both the epidermal growth factor (EGF) receptor and the neu vertebrate proteins. We have examined the possibility of deregulating the tyrosine kinase activity of DER by introducing structural changes which mimic the oncogenic alterations in the vertebrate counterparts. Substitution of valine by glutamic acid in the transmembrane domain, in a position analogous to the oncogenic mutation in the rat neu gene, elevated the in vivo kinase activity of DER in Drosophila Schneider cells sevenfold. A chimera containing the oncogenic neu extracellular and transmembrane domains and the DER kinase region, also showed a threefold elevated activity relative to a similar chimera with normal neu sequences. Double truncation of DER in the extracellular and cytoplasmic domains, mimicking the deletions in the v-erbB oncogene, did not however result in stimulation of in vivo kinase activity. The chimeric constructs were also expressed in monkey COS cells, and similar results were obtained. The ability to enhance the DER kinase activity by a specific structural modification of the transmembrane domain demonstrates the universality of this activation mechanism and strengthens the notion that this domain is intimately involved in signal transduction. These results also support the inclusion of DER within the tyrosine-kinase receptor family.
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PMID:Enhancement of tyrosine kinase activity of the Drosophila epidermal growth factor receptor homolog by alterations of the transmembrane domain. 197 62

Amplification of the HER-2/neu proto-oncogene in breast cancer has been reported to correlate with poor patient prognosis. The proliferation, or growth fraction, of cells has also been shown to be of prognostic importance in breast cancer. A study was conducted to evaluate the correlation between HER-2/neu gene expression and proliferation in breast cancer. Quantitative immunohistochemical methods for the detection of the HER-2/neu protein expression and for assessing the proliferation fraction on frozen sections of tumor cells were used. The detection of epidermal growth factor receptor (EGFR) along with quantitative DNA ploidy analysis, also was performed on the same breast cancers. The results indicated two subgroups of invasive ductal carcinoma; 1) HER-2/neu overexpressing cases that were negative for EGFR expression and had low proliferation fraction, and a tetraploid DNA pattern (22 cases), and 2) other combinations of HER-2/neu expression and EGFR expression, with a high proliferation fraction and an aneuploid DNA pattern (38 cases). Eight cases of carcinoma in situ were positive for HER-2/neu overexpression and negative for EGFR expression, and had a high proliferation fraction and a tetraploid DNA pattern. Twenty-six cases of low-grade carcinoma exhibited low proliferation and a diploid DNA pattern.
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PMID:HER-2/neu oncogene expression and proliferation in breast cancers. 197 97

The HER-2/neu proto-oncogene is homologous with, but distinct from, the epidermal growth factor receptor. Current evidence indicates that this gene is frequently amplified and/or overexpressed in some human breast and ovarian cancers and that these alterations may be clinically important; however, little is known about the expression pattern of the gene in normal tissues. Using immunohistochemistry and northern blot analyses to identify the HER-2/neu protein and transcript respectively, we have evaluated a variety of normal adult and fetal tissues for HER-2/neu expression. HER-2/neu protein was identified on cell membranes of epithelial cells in the gastro-intestinal, respiratory, reproductive, and urinary tract as well as in the skin, breast and placenta. Northern hybridization confirmed the presence of the 4.5 kb transcript encoding the protein in these tissues. The amount of HER-2/neu message and protein was generally higher in fetal tissues than in the corresponding normal adult tissues. HER-2/neu expression levels in these normal tissues were similar to the levels found in non-amplified, non-overexpressing breast cancers and breast cancer cell lines. Southern hybridization of extracted DNA showed that none of the normal tissues expressing HER-2/neu had amplification of the gene. These results confirm that HER-2/neu is normally a membrane constituent of a variety of epithelial cell types.
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PMID:Expression of the HER-2/neu proto-oncogene in normal human adult and fetal tissues. 197 30

Monoclonal antibodies were used to localize immunohistochemically epidermal growth factor receptor and HER-2/neu in normal and neoplastic frozen tissue samples from the lower genital tract of women. In squamous epithelia of the cervix, vulva, and vagina, epidermal growth factor receptor and HER-2/neu both were expressed most strongly by basal keratinocytes. Expression of both of these cell surface molecules decreased as cells underwent differentiation toward the mucosal surface. In contrast, both epidermal growth factor receptor and HER-2/neu were expressed throughout the entire thickness of the epithelium by undifferentiated squamous cells in squamous metaplasia, raised condyloma, and carcinoma in situ. In 34 squamous cancers of the cervix, vulva, and vagina, all malignant cells were found to have moderate to heavy staining for epidermal growth factor receptor. Staining of 33 of these cancers for HER-2/neu was light, although one patient who presented with distant metastases had heavy staining for HER-2/neu. These data suggest that although overexpression of HER-2/neu in squamous cancers of the lower genital tract is a rare event, it may be associated with aggressive biologic behavior.
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PMID:Expression of epidermal growth factor receptor and HER-2/neu in normal and neoplastic cervix, vulva, and vagina. 197 42

The Mr 185,000 glycoprotein encoded by human c-erbB-2/neu/HER2 gene, termed c-erbB-2 gene product, shows a close structural similarity with epidermal growth factor receptor and is now regarded to be a growth factor receptor for an as yet unidentified ligand. Abundant c-erbB-2 mRNA was demonstrated by Northern blot studies in the human breast cancer cell line SK-BR-3. Cellular radiolabeling experiments followed by immunoprecipitation with three different anti-c-erbB-2 gene product antibodies, recognizing extracellular domain, kinase domain, and carboxyl-terminal portion, respectively, demonstrated the production of a large amount of c-erbB-2 gene product which had the capacity to be phosphorylated. Immunization of mice with concentrated culture medium conditioned by SK-BR-3 cells always generated antibodies against c-erbB-2 gene product, demonstrating that this culture medium contained substance(s) immunologically indistinguishable from c-erbB-2 gene product. This observation was supported by the successful development of a monoclonal antibody against c-erbB-2 gene product, GFD-OA-p185-1, by immunizing mice with this culture medium. The biochemical nature of the substance(s) present in the culture medium was further characterized. When the culture medium conditioned by [35S]cysteine-labeled SK-BR-3 cells was immunoprecipitated by three different anti-c-erbB-2 gene product antibodies, only the antibody recognizing extracellular domain precipitated the [35S]-labeled protein with a molecular weight of 110,000, namely p110. The newly developed monoclonal antibody also immunoprecipitated this protein.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The presence of c-erbB-2 gene product-related protein in culture medium conditioned by breast cancer cell line SK-BR-3. 198 Nov 43

Overexpression of the erbB-2/neu gene is frequently detected in human cancers. When overexpressed in NIH 3T3 cells, the normal erbB-2 product, gp185erbB-2, displays potent transforming ability as well as constitutively elevated levels of tyrosine kinase activity in the absence of exogenously added ligand. To investigate the basis for its chronic activation we sought evidence of a ligand for gp185erbB-2 either in serum or produced by NIH 3T3 cells in an autocrine manner. We demonstrate that a putative ligand for gp185erbB-2 is not contained in serum. Chimeric molecules composed of the extracellular domain of gp185erbB-2 and the intracellular portion of the epidermal growth factor receptor (EGFR) did not show any transforming ability or constitutive autophosphorylation when they were expressed in NIH 3T3 cells. However, they were able to transduce a mitogenic signal when triggered by a monoclonal antibody directed against the extracellular domain of erbB-2. These results provide evidence against the idea that an erbB-2 ligand is produced by NIH 3T3 cells. Furthermore, we obtained direct evidence of the constitutive enzymative activity of gp185erbB-2 by demonstrating that the erbB-2 kinase remained active in a chimeric configuration with the extracellular domain of the EGFR, in the absence of any detectable ligand for the EGFR. Thus, under conditions of overexpression, the normal gp185erbB-2 is a constitutively active kinase able to transform NIH 3T3 cells in the absence of ligand.
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PMID:The normal erbB-2 product is an atypical receptor-like tyrosine kinase with constitutive activity in the absence of ligand. 198 8

Expression of the c-erbB-2 gene product and the epidermal growth factor receptor (EGF-R) was investigated in 54 cases of human bladder cancer immunohistologically and by Western blot analysis. For detection of the c-erbB-2 product, two specific antibodies, a rabbit polyclonal antibody directed to the intracellular domain and a murine monoclonal antibody recognizing an epitope in the extracellular domain, were used. Seventeen cases of bladder cancer were stained by the anti-c-erbB-2 polyclonal antibody, while 20 cases were stained by the monoclonal antibody, with good correlation on both stainings (p less than 0.01). There were four c-erbB-2 positive cases in 26 G1 tumors, four in 15 G2 tumors, and nine in 13 G3 tumors. There were also eight erbB-2 positive cases in nine muscle-invasive tumors, nine of 45 superficial tumors, four of five with lymph node metastasis, and seven of 14 without metastasis, as revealed by staining with the polyclonal antibody. Thus, the c-erbB-2 gene product was more frequently expressed in high grade tumors (p less than 0.01), in high stage tumors (p less than 0.01), and nodal metastatic tumors (N.S. by Chi-square test). Twenty-two of the 54 tumors were stained by an anti-EGF-R monoclonal antibody, 528 IgG. The expression of EGF-R was independent of histological grading, tumor stage, and nodal status, and no correlation was observed between expression of the c-erbB-2 product and EGF-R. The c-erbB-2 product may be applicable as a tumor marker for evaluation of malignant potential, invasiveness, and probably metastatic potential of human bladder cancer.
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PMID:Expression of c-erbB-2 gene product in urinary bladder cancer. 198 41

A series of molecular changes are now known to be seen in human pancreatic neoplasia, including the very frequent mutational activation of Kirsten ras oncogene at codon 12, overexpression of the epidermal growth factor receptor, and abnormalities of c-erbB-2 expression. In order to determine whether similar changes can be seen in animal models of pancreatic cancer a molecular analysis of tumours induced in rats by pancreaticobiliary diversion was performed. The polymerase chain reaction was used to amplify portions of the rat Kirsten ras gene and sequence specific oligonucleotide hybridisation was used to define whether sequences were wild type or mutant. No evidence of mutation was found in the Kirsten ras gene at codons 12 or 61, where activating mutations are known to occur. In addition immunohistochemical methods were used to investigate expression of c-erB-2 and the epidermal growth factor receptor but no evidence of abnormal expression was found. We conclude that there are major molecular differences between human and experimental rat pancreatic cancer.
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PMID:Molecular differences between human and experimental pancreaticobiliary diversion-induced rat pancreatic neoplasia. 204 Apr 77

Recently cervical cancer is defined as a sexually-transmitted disease, and human papillomavirus (HPV) has been focused as one of its etiologic agents. It is known that cervical cancer is extraordinarily rare in non-human mammals that have the estrous cycle. In contrast, cervical cancer is frequent in human beings which have lost the estrous cycle, and subsequently evolved a sexual behavior irrespective of the menstrual phase. Therefore, upon the hypothesis that the estrous cycle is a period protected from a sexually transmitted disease, we studied the status of local defence mechanism and growth/differentiation of normal cervical epithelium during the menstrual cycle and pregnancy. Then, the influence of HPV-infection on the growth and differentiation of cervical epithelium was analyzed. As a local immune system of the cervix, both IgA and IgG are secreted in the cervical mucus, and the levels in the follicular phase were significantly higher than those during the luteal phase and pregnancy. An existence of local defence mechanism in the follicular phase is suggested. Analysis of a cell proliferation antigen Ki-67 in normal cervix revealed that parabasal cells enter the cell cycle more frequently in the luteal phase than in the follicular phase. Basal and reserve cells are usually resting, but a few cells enter the cell cycle during the luteal phase and during pregnancy. Since cycling cells are more susceptible to viral infection, the basal and/or reserve cells during the luteal phase and pregnancy are suggested to be under the risk for HPV infection. As factors regulating growth and differentiation of cervical squamous epithelium, immunohistochemical expression of estrogen receptor (ER), progesterone receptor (PR), epidermal growth factor receptor (EGFR), c-erbB-2 protein, adult T-cell leukemia-derived factor (ADF), and HPV DNA was examined. In normal cervix, basal cells were usually ER-positive and PR-negative. Parabasal cells were ER-positive and PR-negative in the follicular phase, while they were ER-negative and PR-positive during the luteal phase and pregnancy. Considering the results of Ki-67 expression, the ER-negative and PR-positive status is possibly related to the proliferation of the cervical squamous epithelium. In cervical condylomas, basal cells infected by HPV6/11 were ER-positive, but HPV16/18-infected cells were ER-negative. Neoplastic cells of CINs and invasive squamous carcinomas containing HPV DNA 16/18 were ER-negative, while those containing HPV DNA 31/33/35 were weakly ER-positive. PR was positive in 2 of 2 condylomas, 18 of 26 CINs, and 13 of 22 invasive carcinomas.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Studies on pathogenesis of cervical carcinoma based on the analysis of growth and differentiation mechanism of cervical epithelium]. 217 18


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