Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:O76050 (neu)
 3,969 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A number of primary human breast carcinomas exhibit amplification of the chromosome 11 region containing the int-2/fgf-3 proto-oncogene, and progression of breast cancer has been correlated with int-2 amplification or with certain restriction fragment length polymorphisms (RFLPs) of the int-2 gene. Using the polymerase chain reaction (PCR), we obtained the int-2 coding sequences from six primary tumors, four of which exhibited amplification of the int-2 gene and one of which exhibited amplification of the neu gene. The majority of these tumors (five of six) were aggressive, as judged by their early recurrence, metastasis, or both. Nucleotide sequencing of PCR products revealed that previously described BamHI and PstI RFLPs of the int-2 gene, as well as a new polymorphism at position 9154, were located within the intron between the second and third exons. A seventh tumor was used to localize one of the PstI RFLPs 5 bp from the splice-acceptor site of the third exon. However, none of the tumor DNAs analyzed showed differences in the int-2 protein coding regions when compared with normal placenta DNA. These results imply that aggressive human breast cancers encode an unaltered form of the int-2 protein.
 ...
PMID:Sequence analysis of the int-2/fgf-3 gene in aggressive human breast carcinomas. 136 93

HER-2/neu gene expression, DNA ploidy and proliferation index were studied in 250 cases of breast cancer. Expression of HER-2/neu was determined by using an antibody to the HER-2/neu receptor. Ki-67 antibody was used to determine the proliferation index of the breast cancers, and the Feulgen method was used to assess DNA amounts in the tumor cells. Histochemical staining was quantitated by image analysis. Of the cancers studied, 72 were positive for overexpression of HER-2/neu protein; of these, 62 (86%) possessed near-tetraploid DNA content, and 47 (65%) had more than one G0G1 stem line (polyploid) of DNA distribution. Cells from the cases negative for HER/2-neu overexpression contained DNA amounts that ranged from diploid to varying degrees of aneuploid. A significant difference in the amounts of cellular proliferation in HER-2/neu overexpressing cancers was found between those that expressed the HER-2/neu receptor on their membranes and those that exhibited mainly cytoplasmic receptors.
 ...
PMID:HER-2/neu oncogene expression, DNA ploidy and proliferation index in breast cancer. 136 46

The erb B2/neu oncogene encodes a protein which sequence is closely similar to the epidermal growth factor receptor (EGFR). We have previously found that EGF can induce the expression of erb B1/EGFR gene in normal and 3H-TdR transformed C3H/10T1/2CL8 mouse embryo fibroblast cells i.e. NC3H10 and TC 3H10 respectively, but we do not know whether the neu oncogene expression can be induced by EGF. In this study, the effect of EGF on NC3H10 and TC3H10 has been observed by Northern blot analysis. The result indicated that EGF had a obvious induction effect on neu oncogene expression in these cells. Thus, the expression of both erbB 1/EGFR gene and erbB 2/neu oncogene can be induced by EGF. This result may provide a novel clue to the molecular mechanism of EGF action in cell nucleus.
 ...
PMID:[The effect of epidermal growth factor on the expression of erb B2/neu oncogene in mouse embryo fibroblast cells]. 136 54

We have developed a system that allows the expression of a single copy of an antibody Fab molecule on the surface of the filamentous bacteriophage M13 and demonstrate the utility of this system for enrichment of specific "Fab phage". A "humanized" version of antibody 4D5 (h4D5) directed against the extracellular domain of the HER2 (neu) receptor, was used as prototype to assess the assembly of Fab molecules on the phage and to determine the power of the enrichment system. The h4D5 Fab phage showed specific binding to the extracellular domain of the receptor and exhibited an affinity for its antigen virtually identical to the Fab itself. By virtue of its antigen binding, the h4D5 Fab phage could be sorted from a million-fold excess of non-cognate Fab phage in only two rounds of sorting. Further experiments demonstrated that the h4D5 Fab phage could be preferentially enriched from mixtures of variant Fab phages that had lower affinities for the HER2 receptor.
 ...
PMID:Fab assembly and enrichment in a monovalent phage display system. 136 62

The over-expression of the proto-oncogene HER-2 (c-erbB-2/neu) in ovarian, endometrial and mammary carcinoma is an important indicator for poor prognosis. We have previously shown in 3 out of 4 ovarian carcinoma cell lines an interferon-gamma (IFN-gamma)-mediated reduction in HER-2 specific protein and RNA levels. The oncogene expression was lowered only in the ovarian carcinoma cell lines but not in 3 IFN-gamma-sensitive human breast cancer cell lines. We extended our observations also to IFN type I, alpha and omega. The expression of the oncogene was measured by both the p185HER-2 ELISA and in selected cases by a living cell radioimmunoassay using the monoclonal antibody (MAb) 4D5 against the extracellular domain. Both IFN types reduced the expression of HER-2 in the ovarian carcinoma cell lines OVCAR-3, HTB-77, 2774 and SKOV-6, and in the SKUT-2 endometrial carcinoma cells. In contrast, SKOV-8 human ovarian carcinoma cells were sensitive for both IFN types regarding proliferation, but only IFN-gamma reduced proto-oncogene expression. In the SKBR-3 human mammary carcinoma cells, neither IFN type had an effect on HER-2 expression. The antibodies 4D5, 7C2, 3E8, and 3H4 which bind to the extracellular domain of p185HER-2 protein specifically inhibited anchorage-independent growth of SKBR-3 and HTB-77 cells. Expression of the oncogene HER-2 is the leading prognostic factor in ovarian cancer. Its modulation might represent a mechanism by which IFNs inhibit cell proliferation.
 ...
PMID:Effects of interferons on the expression of the proto-oncogene HER-2 in human ovarian carcinoma cells. 137 Feb 27

The neu gene, which encodes a putative tyrosine kinase growth factor receptor termed p185neu, was originally identified as a dominant transforming gene in neurogliomas and schwannomas induced by transplacental treatment of rat embryos with ethylnitrosourea. The present studies were undertaken to determine the expression pattern of the neu gene in peripheral nerve. Northern blot analysis of total RNA isolated from rat sciatic nerves demonstrated prominent neu mRNA expression on postnatal days 1 and 7, with substantially lower expression up to adulthood. Immunohistochemical studies confirmed expression of p185neu by Schwann cells (SC) in developing sciatic nerve and minimal p185neu immunoreactivity in adult nerves. However, neu mRNA and p185neu protein progressively increased following sciatic nerve transection in adult animals. In addition, neu mRNA and p185neu were found in neonatal rat sciatic nerve SC and several SC-derived cell lines. In resting SC, neu mRNA was expressed at a low level, but was greatly increased by treatment with forskolin and glial growth factor. These studies demonstrate that the neu gene and its protein product, p185neu, are expressed by SC both in vivo and in vitro and suggest that p185neu plays a role in the regulation of SC proliferation or differentiation.
 ...
PMID:Expression of the neu proto-oncogene by Schwann cells during peripheral nerve development and Wallerian degeneration. 137 76

We have taken a transgenic approach in an effort to specifically transform oligodendrocytes, the myelinating glial cells of the central nervous system (CNS). Transgenic mice were generated with a DNA construct that contained the activated neu oncogene under the transcriptional control of the myelin basic protein (MBP) gene. The MBP/c-neu transgenic animals have experienced a low incidence of brain tumors that express molecular markers specific to oligodendrocytes, providing a mouse model to study the formation and progression of oligodendrocyte tumors. A tumor from a transgenic animal has been dispersed in culture, and transformed cells that express properties of oligodendrocytes and astrocytes have been maintained. The degree to which these cells express phenotypic characteristic of oligodendrocytes or astrocytes is influenced by culture conditions. These transformed cells should serve as a valuable resource with which to study various molecular and biochemical aspects of the myelination process, as well as the lineage interrelationship of CNS glial cells.
 ...
PMID:Expression of the neu oncogene under the transcriptional control of the myelin basic protein gene in transgenic mice: generation of transformed glial cells. 137 83

Two new breast carcinoma cell lines, designated as UISO-BCA-1 and UISO-BCA-2, have been established from pleural effusions of postmenopausal women. Both cell lines show properties of mammary epithelial cells, such as positive immunoreactivity to cytokeratins and human milk fat globulin, presence of desmosomal junctions, numerous microvilli, intracytoplasmic duct-like vacuoles and tonofilaments. UISO-BCA-1 and UISO-BCA-2 cells differ from each other with respect to cellular morphology, ultramicroscopic details, immunoreactivity to Her-neu oncogene protein, chromosomal mode and in vivo and in vitro growth rates. UISO-BCA-1 cells are well-differentiated (as evident from their morphology and ultrastructural details) and hyperploid (42-114 chromosomes). In vitro, UISO-BCA-1 cells are fast growing, with a population doubling time of 31.2 +/- 9.6 hrs (n = 4), and are tumorigenic (100%) in athymic nude mice. In contrast, UISO-BCA-2 cells are poorly differentiated, but are also hyperploid, with 54-64 chromosomes. UISO-BCA-2 cells are slow growing in vitro (population doubling time: 56.0 +/- 5.0 hrs [n = 4]) and have limited tumorigenic potency (20-40%). Both these cell lines are estrogen and progesterone receptor (less than 10 fmol/mg protein) negative.
 ...
PMID:Human breast carcinoma cell lines: ultrastructural, genotypic, and immunocytochemical characterization. 137 94

The antigen MUSE11 detected by a monoclonal antibody (MAb) is an adenocarcinoma-associated antigen, while CA15-3 is a representative breast cancer-associated antigen detected by MAbs 115D8 and DF3. MAb MUSE11 showed higher binding activity to a synthetic peptide corresponding to the tandem repeat motif of the mucin core protein than that of MAb DF3, although MAb DF3 also had a significant binding activity indicating that MAbs MUSE11 and DF3 could recognize an identical polypeptide core. The reactivity of MAb DF3 to a breast cancer cell line MRK-neu-1 was completely abolished by neuraminidase treatment whereas that of MAb MUSE11 was partly conserved. The simultaneous measurement of the antigens MUSE11 and CA15-3 in sera from 35 cancer patients demonstrated that the incidence of abnormal serum level of CA15-3 was lower than that of antigen MUSE11. These data suggest that at least a part of the structural basis for the difference between the serum levels of antigen MUSE11 and CA15-3 could be carbohydrate side chains including sialic acids.
 ...
PMID:Circulating tumor-associated antigens detected by monoclonal antibodies against the polypeptide core of mucin--comparison of antigen MUSE11 with CA15-3. 137 32

Enhanced levels of disulfide-linked dimers of the neu oncogene product have been suggested to be associated with the transformed state [Weiner DB, Liu J, Cohen JA, Williams WV, Greene MI: Nature 338:230-231, (1989)]. We, therefore, investigated the properties of the dimeric forms of p185HER-2/neu from the human breast carcinoma cell line, SK-BR-3. We found disulfide-linked dimers as well as noncovalently associated dimers that were detected by cross-linking with bis(sulfosuccinimidyl) suberate (BS3). However, the disulfide-linked dimers did not exist in intact cells, since they were eliminated when the cells were lysed in the presence of the alkylating agent, sodium iodoacetate. Moreover, the disulfide-linked dimeric molecules were not the activated form of p185HER-2 since they incorporated about the same level of phosphate in an in vitro kinase reaction as the monomeric molecules. In contrast, the noncovalent dimers appeared to be present on the surface of intact cells and were phosphorylated at levels at least tenfold higher than monomers in an in vitro kinase reaction.
 ...
PMID:Disulfide-linked and noncovalent dimers of p185HER-2 in human breast carcinoma cells. 137 5


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>