Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.10.1 (ERK)
 95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The activation of ERBB oncogenes has been described in various human tumours, including squamous cell carcinomas of the head and neck (SCCHN), and, in some of them, it has been correlated with a poor prognosis. Tissue samples from 59 patients with SCCHN were studied. After DNA extraction, the ERBB1, ERBB2 and ERBB3 copy number in tumour samples was estimated with the polymerase chain reaction (PCR) method. The PCR products were analysed by agarose gel electrophoresis and quantified by image analysis techniques. 9 (15%) cases presented with ERBB1 amplification, which was correlated with lymph node involvement (P = 0.04), poorly differentiated tumours (P = 0.03) and a hypopharyngeal primary site (P = 0.035). No correlation among amplification status, recurrence, metastases and survival was observed, although this may be due to the small number of patients in the amplified group. None of the 59 cases presented amplification of ERBB2 and ERBB3 oncogenes.
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PMID:Amplification of ERBB oncogenes in squamous cell carcinomas of the head and neck. 894 88

Patients with previously untreated squamous cell lung carcinomas were evaluated to see if combining the expression of molecular and cellular factors with the most important clinical prognostic factors could improve the diagnostic ability to predict prognosis. For this reason, immunohistochemistry was used to examine the squamous cell lung carcinomas from 121 patients for their expression of ERBB-1, vascular endothelial growth factor (VEGF), cyclin A, FOS, JUN and MYC. Median survival was shorter for patients with ERBB-1-, VEGF-, cyclin A-, FOS-, or JUN-positive tumours. For those patients with positive lymph node involvement, the survival times were also shorter in the VEGF-positive, cyclin A-positive and FOS-positive groups. Multivariate analysis independently demonstrated a significant prognostic value for lymph node involvement, VEGF and FOS.
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PMID:Prognostic value of ERBB-1, VEGF, cyclin A, FOS, JUN and MYC in patients with squamous cell lung carcinomas. 948 27

The molecular genetic events involved in the etiology of human granulosa cell (GC) tumors, which represent approximately 7% of all malignant ovarian neoplasms, are unknown. Amplification and/or overexpression of the ERBB genes are a feature of many cancer types, and overexpression of erbB2 correlates with poor prognosis in epithelial ovarian cancer. In the present study, we used immunohistochemistry to determine the level and frequency of expression of different erbB receptors in GC tumors. Ten of 12 tumors expressed erbB4 at moderate to high levels in >50% of cancer cells, whereas erbB2 (6 of 12) and erbB3 (2 of 12) were expressed less frequently. Western blot experiments showed that the only available GC tumor cell line, COV434, also expressed erbB receptors. Heregulin (HRG)-beta2, a ligand for erbB3 and erbB4 receptors, stimulated tyrosine phosphorylation of the erbB receptors, which was accompanied by activation of Erk1 and Erk2, two mitogen-activated protein kinases with a functional role in mitogenesis. Importantly, HRG increased cell proliferation in COV434 cells, and treatment with HRG/PE40, a ligand toxin shown previously to be cytotoxic against human breast cancer cells overexpressing erbB receptors, led to a dramatic and irreversible decrease in cell number. These results indicate that erbB receptor signaling pathways may be critical in the control of GC tumor cell proliferation and that HRG/PE40 is a potential therapeutic agent for the treatment of GC tumors.
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PMID:Granulosa cell tumors express erbB4 and are sensitive to the cytotoxic action of heregulin-beta2/PE40. 958 10

The complex system of ERBB receptors and ligands is implicated in growth and differentiation of the mammary gland. However, it has not been comprehensively examined in this dynamic tissue. Combined RNA and protein analyses of glands in different stages from virgin to involution revealed differential expression of the four ERBB receptors, as well as distinctive patterns of ERBB ligand expression that suggested specialized function. ERBB localization was linked to mammary gland function. Thus, in the virgin gland, ERBB1 and ERBB2 were colocalized to all major cell types during ductal morphogenesis but differentially localized in the mature gland. All four ERBB receptors were restricted to epithelia in the differentiated gland. Analyses of ERBB tyrosine phosphorylation provided strong evidence of interaction between the four receptors in this physiological context. Thus, exogenous EGF induced stage-dependent transphosphorylation of ERBB2-4 as well as ERBB1, whereas endogenous phosphorylation of all four receptors peaked in late pregnancy and lactation.
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PMID:Dynamic expression and activation of ERBB receptors in the developing mouse mammary gland. 966 64

Seven cases of myelogenous leukemia--two acute erythroleukemia (AEL), four acute myelogenous leukemia (AML), and one acute myelomonocytic leukemia (AMMoL)--were found in 22 members of three consecutive generations of a family in the past 16 years (1973-1989). By using cytogenetic, hematologic, and biochemical analyses of those surviving in this family, we also found four members who might develop leukemia in the future. Southern blot analysis of one of the four members and her father (an acute leukemia patient) with a v-ERBB probe showed that the gene abnormalities consisted of a c-ERBB rearrangement (hereditary) and a rearrangement/amplification of the same gene.
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PMID:Genetic studies on a family with acute myelogenous leukemia. 1068 40

Rearrangement and coamplification of the 8p12 and 11q13 chromosomal regions occurs in a significant proportion of breast cancers. It usually involves a complex hybrid structure in which the FGFR1 and CCND1 genes are amplified. We report here a different type of 8p12-11q13 rearrangement in the MDA-MB-175 mammary carcinoma cell line. This amplification contains the NRG1/HGL (from 8p12-21) and DOC4 (from 11q13) genes, encoding respectively a ligand for ERBB receptors and a stress-induced protein which is a mammalian ortholog of Drosophila Tenm/Odz. It has been shown previously (Wang et al, Oncogene 18: 5718-5721, 1999) that these two genes are rearranged and fused by a translocation event. This type of event was not found in 30 tumors tested that showed coamplification of the 8p12 and 11q13 regions.
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PMID:Translocation and coamplification of loci from chromosome arms 8p and 11q in the MDA-MB-175 mammary carcinoma cell line. 1071 35

The ERBB receptors have a crucial role in morphogenesis and oncogenesis. We have identified a new PDZ protein we named ERBIN (ERBB2 interacting protein) that acts as an adaptor for the receptor ERBB2/HER2 in epithelia. ERBIN contains 16 leucine-rich repeats (LRRs) in its amino terminus and a PDZ (PSD-95/DLG/ZO-1) domain at its carboxy terminus, and belongs to a new PDZ protein family. The PDZ domain directly and specifically interacts with ERBB2/HER2. ERBIN and ERBB2/HER2 colocalize to the lateral membrane of human intestinal epithelial cells. The ERBIN-binding site in ERBB2/HER2 has a critical role in restricting this receptor to the basolateral membrane of epithelial cells, as mutation of the ERBIN-binding site leads to the mislocalization of the receptor in these cells. We suggest that ERBIN acts in the localization and signalling of ERBB2/HER2 in epithelia.
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PMID:ERBIN: a basolateral PDZ protein that interacts with the mammalian ERBB2/HER2 receptor. 1087 17

ERBB family receptor tyrosine kinases are overexpressed in a significant subset of breast cancers. One of these receptors, HER2/neu, or ErbB-2, is the target for a new rational therapeutic antibody, Herceptin. Other inhibitors that target this receptor, and another family member, the epidermal growth factor (EGF) receptor, are moving into clinical trials. Both of these receptors are sometimes overexpressed in breast cancer, and still subject to regulation by hormones and other physiological regulators. Optimal use of therapeutics targeting these receptors will require consideration of the several modes of regulation of these receptors and their interactions with steroid receptors.
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PMID:Tyrosine kinase signalling in breast cancer: ErbB family receptor tyrosine kinases. 1125 Jul 7

In most of the studies about molecular alterations in squamous cell carcinomas of the head and neck there is not distinction between the different subsites of this area. The objective of this study is to describe the molecular alterations in squamous cell carcinomas of the oropharynx. Twenty-nine oropharyngeal carcinomas, with a minimum follow-up of 36 months, were studied. The molecular alterations analyzed were: the amplification of 11q13 region (in the 29 cases), and the MYC and ERBB1 oncogenes (in 22 cases); the integration of Human Papillomavirus (HPV) types 6b and 16 (in 22 cases); the loss of heterozygosity (LOH) of p53 and N-acetyltransferase-2 (NAT2) gene (in 12 and 13 informative cases, respectively); and the cellular DNA content (in 13 cases). The most frequent alterations found were the LOH at p53 (67%), and NAT2 (54%) locus, followed by 11q13 amplification (49%). ERBB1 amplification was found in 14% of the cases, and MYC amplification only in one (5%). Integration of the HPV was found in 23% of the cases. Nine (69%) of the 13 analyzed cases were aneuploid. The only alteration with a prognostic significance was 11q13 amplification that showed a tendency to be associated with a higher frequency of nodal metastases and tumor recurrence.
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PMID:[Molecular changes in epidermoid carcinoma of the oropharynx]. 1126 75

To investigate the expression of human papillomavirus type 16 (HPV-16) E5 protein in squamous neoplastic changes in the uterine cervix, the specific E5 antibody was generated and used to identify the expression of E5 protein in 40 cases of HPV-16-positive tissues and 5 previously identified HPV-negative normal cervical tissues. The results revealed that E5 protein was primarily expressed in the lower third of the epithelium in low-grade squamous intraepithelial lesions (SILs) and throughout the whole epithelium in high-grade SILs. In invasive squamous carcinoma, 60% of HPV-16-infected cancers which contained the episomal viral genome had the E5 gene, and could express E5 protein which was located throughout the whole epithelium. Previously, we documented the expression of type I growth factor receptors [ERBB1/EGFR (epidermal growth factor receptor), ERBB2, ERBB3 and ERBB4] in the full range of cervical neoplasias by immunohistochemistry assay. Hence, in this study, we extensively analyzed the correlation between the expression of E5 protein and the expression of type I growth factor receptors. Among 40 HPV-16- infected cervical neoplasias, we found that the expression of E5 protein was significantly correlated with either the expression of the ERBB1 or the ERBB4 receptor.
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PMID:The expression of HPV-16 E5 protein in squamous neoplastic changes in the uterine cervix. 1128 52


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