Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04626 (erbB-2)
 5,251 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The discovery of peptide growth factors and cancer-causing genes (oncogenes and tumor-suppressor genes) has provided us with the exciting opportunity to begin to understand the molecular pathology of human ovarian cancer. Activation of several genes, including HER-2/neu, myc, ras, and p53 have been described in some ovarian cancers. In addition, some protooncogenes such as the epidermal growth factor receptor (erbB) and the M-CSF receptor (fms) are expressed along with the respective ligands (peptide growth factors) in some ovarian cancers. Although the studies reviewed in this paper represent a promising beginning, we remain far from a comprehensive understanding of growth regulation and transformation of human ovarian epithelium.
 ...
PMID:Growth regulation and transformation of ovarian epithelium. 842 Jun 75

We are only beginning to understand the importance of lung cancer tumor biology in relation to prognosis and response to therapy. Many of the biologic and genetic changes we have described are preliminary observations and require further confirmation before clinical use. However, information concerning three oncogenes may soon prove to be helpful in the clinical arena: the myc genes in SCLC, and the ras genes and c-erbB-2 in NSCLC. In general their presence identifies poor patient response to therapy and poor survival. These markers are currently being used in a clinical setting at some research centers, but are not recommended for general diagnostic or prognostic use without further confirmation of their utility. Incorporation of this information with that learned by standard staging procedures may result in improved understanding of patient prognosis and challenge current concepts of lung cancer treatment. For example, surgically resected stage I NSCLC patients may benefit from adjuvant therapy if found to have these adverse biologic factors, and require more stringent follow-up after therapy. Finally the understanding of the pathogenesis of lung cancer may enable the development of novel therapy directed against these growth pathways. Our ultimate goal is to derive a therapeutic and prognostic paradigm involving both molecular-genetic and clinical factors to arrive at an optimal staging model and treatment plan.
 ...
PMID:Oncogenes and growth factors in human lung cancer. 846 46

Evidence is presented that the cytoplasmic domain of the type I interleukin-1 receptor (IL-1R) may be a GTPase. This domain conserves segments of hydrophobic amino acids that suggest a structural relatedness to the ras protooncogene protein and other members of the GTPase superfamily, despite a lack of significant detectable sequence homology. When the hydrophobic segments of the IL-1R were aligned with similar segments of the GTPases, it became apparent that the IL-1Rs possess a number of conserved amino acids that represent plausible functional residues for base-specific binding of GTP, magnesium chelation, and phosphate ester hydrolysis. Furthermore, a segment of five contiguous residues were found that is identical between ras and the IL-1R, and which is positioned to form part of the guanine base binding pocket. If this model is correct, then the IL-1Rs possess a highly conserved effector protein binding region, but one that is entirely unrelated to the effector regions of other superfamily members. Therefore, if the IL-1R is indeed a GTPase, then its activation function may be directed to as-yet unrecognized effector target proteins, as part of a unique cellular signal transduction pathway.
 ...
PMID:Evidence from sequence information that the interleukin-1 receptor is a transmembrane GTPase. 852 83

Studies of amplification and/or overexpression of c-myc, HER-2/neu, and H-ras in breast cancer have shown that each is associated with a poor prognosis. The purpose of this study was to explore the possibility that there is a preferred sequence of amplification of these oncogenes in breast cancer. The frequencies of amplification and patterns of co-amplification of c-myc, HER-2/neu, and H-ras were studied in a group of 84 breast cancers. The data suggested a preferred sequence of amplification that consisted of c-myc amplification-HER-2/neu amplification-H-ras amplification. This model was supported by loglinear analysis. In addition, the levels of amplification of JC-A, a DNA fragment newly isolated from a patient with advanced breast cancer, were studied in 61 of these cases. The data suggested that JC-A amplification occurred early. Loglinear analysis supported a model in which JC-A amplification occurred either before or after c-myc amplification but was unrelated to Her-2/neu or ras amplification.
 ...
PMID:Assessing sequential oncogene amplification in human breast cancer. 852 65

Human solid tumors accumulate multiple genetic abnormalities as they progress to advanced stages. Multiparameter flow cytometry measurements of individual cells within each tumor may be useful in describing the genetic pathways taken by individual tumors during the course of their genetic evolution. In this paper, we analyzed correlated cell-by-cell measurements of cell DNA content, HER-2/neu protein content, and ras protein content obtained by multiparameter flow cytometry studies of primary breast cancers from 92 patients. These laboratory findings were correlated with established clinical prognostic factors for each patient at the time of diagnosis, using a stepwise multiple analysis of variance (MANOVA). The stepwise MANOVA successively splits a group of patients into two mutually exclusive dissimilar groups, selecting the clinical prognostic factor that is most effective in doing so. Using this criterion, formation of the first three groups that were judged most dissimilar on the cytometry parameters was based on the number of positive nodes at the time of diagnosis. We show that ploidy, HER-2/neu protein content, and ras protein content, as measured by multiple parameter flow cytometry, are correlated with nodal status and other known clinical prognostic factors. The cell-by-cell multiparameter data suggest that for some individual tumors there are multiple genetic evolutionary pathways. Multiple genetic evolutionary pathways are also suggested by the MANOVA analysis. Focusing on the identification and analysis of genetic evolutionary pathways within individual tumors and across patients appears to offer a promising approach for defining the prognosis of early cancers.
 ...
PMID:Analytical approaches relating genetic evolutionary pathways to prognostic factors. 852 67

Multiparameter flow cytometry studies were performed on the cells of an aggressive human breast cancer at the time of diagnosis and at relapse. The aneuploid cells that overexpressed large amounts of both HER-2/neu and ras survived intensive chemotherapy and were responsible for tumor relapse. At relapse, these cells were shown to overexpress simultaneously at least five oncogenes: HER-2/neu, ras, EGF receptor, p53 and c-myc. A partial reconstruction of the genetic evolutionary sequence in this tumor indicated that HER-2/neu overexpression was an early step in the sequence. Subsequent HER-2/neu overexpression, EGF receptor overexpression and p53 protein overexpression were each associated with ras overexpression. The data suggest that ploidy and oncogene overexpression cannot be used as independent clinical prognostic factors. The ability to characterize tumors according to the degree of advancement in the genetic evolutionary might serve as a basis for genetic staging for adjuvant therapy.
 ...
PMID:Preferred genetic evolutionary sequences in human breast cancer: a case study. 887 61

Breast cancers frequently over-express a number of growth factor receptors. In addition, elevated src family kinase activity is present in a percentage of these neoplasms and has been implicated in signal transduction in these cells. Therefore, inhibiting tyrosine kinase activity is a potential approach for treating these tumors. Utilizing the SKBR3 and MCF-7 breast cancer cell lines, we evaluated the effects of broadly targeting growth factor receptor and cytoplasmic tyrosine kinases with tyrosine kinase inhibitors (herbimycin A and genistein) to inhibit proliferation. We also evaluated these inhibitor's effects on proteins that regulate ras function, which is a convergence point for signaling through both src family kinases and a number of growth factor receptors with tyrosine kinase activity (e.g., epidermal growth factor and erbB-2 receptors). We specifically evaluated whether these compounds affected 2 recently discovered proteins involved in controlling ras function: Shc, which is tyrosine-phosphorylated by src and activated growth factor receptors, and Grb-2, which mediates signal transduction from activated growth factor receptors through ras. We evaluated their effects on tyrosine phosphorylation of Shc, binding of Grb-2 to Shc and MAP kinase activity. Both cell lines were inhibited in a dose-dependent manner by each compound. This was accompanied by decreased Shc tyrosine phosphorylation, Shc's association with Grb-2 and MAP kinase activity. Thus, tyrosine kinase inhibitors can inhibit proliferation of breast cancer cells, accompanied by inhibition of signal transduction steps potentially mediated through ras. Tyrosine kinase inhibitors might, therefore, be useful for the treatment of breast cancer.
 ...
PMID:Effects of tyrosine kinase inhibitors on the proliferation of human breast cancer cell lines and proteins important in the ras signaling pathway. 856 15

The activated neu (HER2/c-erbB-2) oncogene is extremely potent in inducing mammary cancer. For example, neu induces greater than 200 times as many tumors as the activated ras oncogene when directly introduced into in situ rat mammary epithelial cells using replication-defective retroviral vectors. In order to characterize mechanisms underlying this potency, we sought to identify uniquely overexpressed genes in neu-initiated tumors that were not overexpressed in tumors induced by weaker initiating agents, including activated ras and the chemical carcinogens dimethylbenz[a]anthracene and N-nitroso-N-methylurea. Several genes, including those encoding keratin K7 and the u haplotype of MHC class I RT1-A, were found to be overexpressed in neu-initiated carcinomas as well as in mammary carcinomas induced by other agents, when compared to their expression in normal mammary tissue. One gene, however, encoding a member of the lipocalin and calycin protein families, was 12-fold overexpressed in neu mammary tumors and was not overexpressed in ras or chemically induced carcinomas. This uniquely overexpressed gene was termed neu-related lipocalin (NRL). NRL protein was produced in a baculovirus system, purified and used to generate polyclonal antibodies. Western blot analysis indicate that neu-initiated mammary carcinomas express abundant NRL protein when compared to other mammary tumors.
 ...
PMID:Overexpression of neu-related lipocalin (NRL) in neu-initiated but not ras or chemically initiated rat mammary carcinomas. 857 Jan 73

Thirty-two cases of ovarian carcinoma, two of normal ovaries, four of benign epithelial ovarian tumor, and three of borderline epithelial ovarian tumor were studied using Southern blot hybridization of DNA. In 15 of the 32 cases of ovarian carcinoma, peripheral lymphocytes were also studied. The amplification rate of C-myc, C-N-ras, C-Ki-ras and C-erbB-2 in ovarian carcinoma were 50%, 44%, 31% and 25% respectively. The amplification of C-Ki-ras and C-N-ras took place chiefly in cases of early stage and those of good differentiation. The amplification of C-N-ras was also found in cases of advanced stage. The amplifications of C-myc and C-erbB-2 were chiefly found in cases above stage III and those of poor differentiation. A total of 83% of the patients who died were found to have amplifications of more than 2 proto-oncogenes, with which the amplification of C-erbB-2 was involved.
 ...
PMID:Amplifications of proto-oncogenes in ovarian carcinoma. 858 78

Proliferating cell nuclear antigen (PCNA) expression was studied by immunohistochemistry on paraffin-embedded sections of 293 primary colorectal adenocarcinomas and 56 corresponding lymph node metastases. PCNA-positive expression was detected in <25% of tumour cells in 172 (59%) cases and in > 25% in 121 (41%) cases. PCNA accumulation was related to over-expression of c-erbB-2 and p53 and tended to be increased in cases with ras over-expression. PCNA expression was identical in primary and corresponding metastases. No significant relationship was observed between PCNA expression and prognosis and other clinico-pathological variables, including grade of differentiation, growth pattern, Dukes' stage, site, age or sex. We conclude that PCNA expression may be related to alterations of oncoproteins but that PCNA itself could not provide additional information for the development of metastasis and prognosis in colorectal adenocarcinoma.
 ...
PMID:Proliferating cell nuclear antigen (PCNA) in relation to ras, c-erbB-2,p53, clinico-pathological variables and prognosis in colorectal adenocarcinoma. 860 60


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