Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:2.7.10.1 (ERK)
95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A related DNA fragment distinct from the epidermal growth factor receptor and ERBB2 genes was detected by reduced stringency hybridization of v-erbB to normal genomic human DNA. Characterization of the cloned DNA fragment mapped the region of v-erbB homology to three exons with closest identity of 64% and 67% to a contiguous region within the tyrosine kinase domains of the epidermal growth factor receptor and ERBB2 proteins, respectively. cDNA cloning revealed a predicted 148-kDa transmembrane polypeptide with structural features identifying it as a member of the ERBB gene family, prompting us to designate the gene as ERBB3. It was mapped to human chromosome 12q13 and was shown to be expressed as a 6.2-kilobase transcript in a variety of normal tissues of epithelial origin. Markedly elevated ERBB3 mRNA levels were demonstrated in certain human mammary tumor cell lines. These findings suggest that increased ERBB3 expression, as in the case of epidermal growth factor receptor and ERBB2, may play a role in some human malignancies.
...
PMID:Isolation and characterization of ERBB3, a third member of the ERBB/epidermal growth factor receptor family: evidence for overexpression in a subset of human mammary tumors. 268 75

The HER4/erbB-4 gene has been isolated as the fourth member of the human EGFR subfamily of tyrosine kinases and has been reported to encode a receptor for NDF/heregulin. In the present study we determined the chromosomal location of the HER4/erbB-4 gene within the human genome. Using human cDNA probes in fluorescence in situ hybridization (FISH), we mapped the HER4/erbB-4 gene to human chromosome 2q33.3-34. This finding established that also the HER4/erbB-4 gene is located in close vicinity of homeobox and collagen gene loci, as is the case for the related EGFR, erbB-2/neu and erbB-3. Aberrations of this chromosomal region associated with T cell leukemias and lymphomas as well as alveolar rhabdomyosarcomas raise the possibility that HER4/erbB-4 might be activated in these tumour types.
...
PMID:Localization of the human HER4/erbB-4 gene to chromosome 2. 770 Jun 49

The objective of the present study was to determine the frequency of amplifications of three different members of the erbB gene family in human glioblastoma multiforme (GBM). We investigated 47 glial tumors (37 GBM WHO grade IV, 5 anaplastic astrocytomas WHO III and 5 astrocytomas WHO II) by Southern and Western analysis, and immunocytochemistry. Gene amplification of erbB genes in human malignant gliomas was restricted to the EGF receptor (EGFR) gene, erbB-1. We found amplification of the EGFR gene in 49% (18/37) of GBM but not in the astrocytomas WHO II/III. The erbB-2 and erbB-3 genes showed no amplification in the tumor specimens investigated in this study. At the protein level we found overexpression of the EGF receptor in 86% (32/37) by Western analysis and in 92% (34/37) by immunocytochemistry. Expression of the ERBB2 protein was present in 54% (20/37) but immunoreactivity was much weaker than for EGF receptor and in most cases barely detectable by Western analysis and immunocytochemistry. The ERBB3 protein was not expressed in the glial tumors investigated in this study. Of the three erbB genes only gene amplification and overexpression of the EGF receptor seems to have an impact on tumor progression of human gliomas. Our data from immunohistochemistry indicate that ERBB2 expression in GBM is closely correlated with EGF receptor levels and is therefore not useful as an independent prognostic parameter.
...
PMID:Amplification and differential expression of members of the erbB-gene family in human glioblastoma. 776 96

The type 1 family of growth factor receptors includes the EGFR, c-erbB2, c-erbB3, and c-erbB4. All four members of the family are expressed in breast cancer. The EGFR gene and more frequently the c-erbB2 gene are amplified in a proportion of cases. In addition to increased expression as a result of gene amplification, overexpression of perhaps all of the receptors also appears to occur, probably as a result of increased mRNA transcription. Overexpression may have prognostic value and may predict response to current therapies. Finally these GFR proteins represent targets for new types of chemotherapeutic agents.
...
PMID:The type I growth factor receptors in human breast cancer. 791 66

Betacellulin is a member of the epidermal growth factor (EGF) family. These soluble proteins are ligands for one or more of the four receptor tyrosine kinases encoded by the erbB gene family (erbB-1/epidermal growth factor receptor (EGFR), neu/erbB-2/HER2, erbB-3/HER3 and erbB-4/HER4). While evidence suggests that betacellulin is a ligand for the EGFR, the ability of betacellulin to regulate other erbB family receptors has not been analysed. Previously we engineered derivatives of the mouse Ba/F3 hematopoietic cell line to ectopically express erbB family receptors, singly and in pairwise combinations. We have stimulated this panel of cell lines with betacellulin and two other EGF family members, EGF itself and neuregulin-beta (NRG-beta). In the cell lines expressing a single erbB family receptor, betacellulin not only stimulated EGFR tyrosine phosphorylation, but it activated erbB-4 as well. Furthermore, in the double recombinant Ba/F3 derivatives, betacellulin stimulated a complex pattern of receptor phosphorylation distinct from the patterns activated by NRG-beta and EGF. Moreover, betacellulin stimulated a complex pattern of interleukin-3 independence in the Ba/F3 derivatives distinct from those activated by NRG-beta and EGF. These data identify a novel receptor for betacellulin and establish that different EGF family ligands activate distinct patterns of receptor phosphorylation and coupling to cellular signaling pathways.
...
PMID:Betacellulin activates the epidermal growth factor receptor and erbB-4, and induces cellular response patterns distinct from those stimulated by epidermal growth factor or neuregulin-beta. 857 Feb 11

The tyrosine kinase receptor family, including the epidermal growth factor receptor (EGF-R), c-erbB2 and, more recently, the c-erbB3, has been recognized as being of particular importance in many human malignancies. This study was undertaken to define the role of c-erb B2 and c-erbB3 in adenoid cystic carcinomas (A.C.C.) of the salivary glands. Sixteen cases of A.C.C. were studied immunohistochemically, using antibodies against each erbB gene family product. EGF-R was not detected in any of these samples but c-erbB2 and c-erbB3 gene products (ERBB2and ERBB3) were demonstrated in all A.C.C. sections with some degree of straining. Tubular and cribriform patterns overexpressed particularly large amounts of ERBB2 and ERBB3. Strong staining was mainly demonstrated in tumor cells of the invasive area. These results suggested that overexpression of ERBB2 and ERBB3 is related to tumor differentiation and invasion in adenoid cystic carcinomas.
...
PMID:Expression of c-erbB family gene products in adenoid cystic carcinoma of salivary glands: an immunohistochemical study. 866 36

Previously we reported that neu differentiation factor (NDF)/heregulin (HRG) elevates tyrosine phosphorylation of its receptors erbB-3, erbB-4, and erbB-2 (through heterodimer formation). We also showed that both NDF/HRG and antibodies to erbB-2 can arrest growth and induce differentiation in breast cancer cells. In this study, we report on the mechanism of NDF/HRG-induced cellular effects. We show that NDF/HRG and antibodies to erbB-2 receptors up-regulate expression of p53 by stabilizing the protein. This is accompanied by up-regulation of the p53 inducible gene, p21CIP1/WAF1, in a variety of cell lines: MCF7 and their derivatives (MCF7/HER2, MN1 and MCF-7-puro), ZR75T and LnCap cells. The induction of p21 is further enhanced when cells are treated with both NDF/HRG and DNA-damaging chemotherapeutic agents (i.e. doxorubicin). The NDF/HRG mediated induction of p21 is dependent on wildtype p53, as it fails to occur in cells expressing dominant negative p53 (MDD2). Furthermore, p21 induction is capable of inactivating cdk2 complexes as measured by Histone H1 phosphorylation assays. Finally, we show that in primary cultures of breast and other cancers, p21 is significantly induced in response to NDF/HRG treatment. Collectively, these observations suggest that the mechanism of breast cancer cell growth inhibition and differentiation via erbB receptors activation is through a p53-mediated pathway.
...
PMID:Neu differentiation factor (Heregulin) activates a p53-dependent pathway in cancer cells. 870 May 12

ErbB-3 is a member of the epidermal growth factor receptor (EGFR/ErbB) family. In addition to the previously reported 6.2 kb full-length and 1.4 kb truncated c-erbB3 transcripts, we have observed a 1.7 kb c-erbB3 human transcript in Northern blots that specifically hybridizes to a probe of the extracellular domain of the receptor. Using 3'-RACE we have isolated four novel c-erbB3 cDNA clones of 1.6, 1.7, 2.1 and 2.3 kb from a human ovarian carcinoma-derived cell line. All four alternate transcripts are synthesized by readthrough of an intron and use of an alternative polyadenylation signal within this intron. Identical c-erbB3 transcripts are expressed in normal human placental tissues. Expression of these alternate transcripts is tissue-specific as indicated by Northern blot and RNase protection analyses. Fibroblasts transfected with expression vectors carrying these alternate c-erbB3 cDNA clones stably express truncated ErbB-3 products. Three of these four cDNA clones express a receptor product that is secreted. Immunoprecipitation analysis of primary cultures of human ovarian carcinomas also demonstrate the expression of a 90 kDa ErbB-3 related protein that is secreted. Furthermore, we demonstrate conservation of the exon-intron junctions between members of the erbB gene family in those regions of the gene encoding the extracellular domain. This gene structure is also conserved in the c-erbB1 homologues of Drosophila and C. elegans. Growth regulatory roles for related truncated ErbB products recently have been reported. It is, therefore, possible that the products of these four alternate c-erbB3 transcripts may also play important growth regulatory roles in normal and transformed cells.
...
PMID:Isolation and characterization of four alternate c-erbB3 transcripts expressed in ovarian carcinoma-derived cell lines and normal human tissues. 968 22

The expression and coexpression of EGFR, c-erbB-2 and c-erbB-3 in 21 gastric cancers and 20 chronic gastritis was examined using immunohistochemistry on fresh frozen tissues considering clinicopathological variables. Generally, gastric cancer patients showed a higher incidence of EGFR, c-erbB-2 and d-erbB-3 overexpression than the group with chronic gastritis (81% and 43%; 38% and 45%; 35% and 20%, respectively), however, statistically significant differences were found only for EGFR expression (p = 0.01). No association between immunoreactivity of all growth factor receptors and the histopathological structure of gastric cancer was observed. EGFR and c-erbB-3 proteins were detected more frequently in patients with III/IV than in I/II of TNM stages, while c-erbB-2 overexpression was higher in I/II vs. III/IV stages. In chronic gastritis with intestinal metaplasia and or coexisting carcinoma lesions, a higher frequency of the expression of studied proteins was observed in comparison with chronic gastritis without those alternations; however, these differences were statistically insignificant. The percentage of positive cases with coexpression of two proteins was comparable in gastric cancer and chronic gastritis (33% and 35%) but the simultaneous expression of all three receptors was evident only in gastric cancer (19%). Our results indicate that at least one or two members of EGFR related receptors could appear in the early stages of gastric tumorigenesis. The enhancement of c-erbB-2 and c-erbB-3 reactivity seems to cooperate with EGFR activation in the gastric cancer development. Our results indicate the promotional rather than direct transformational role for EGFR supergene family in gastric carcinogenesis.
...
PMID:Expression of epidermal growth factor receptor family proteins (EGFR, c-erbB-2 and c-erbB-3) in gastric cancer and chronic gastritis. 970 36

We examined c-erbB3 and c-erbB4 mRNA expression in 47 primary breast cancer samples by simultaneous RT-PCR and have investigated correlations between these parameters and the expression of both ER and EGFR mRNA and protein as measured by RT-PCR and ICA and with Ki67 immunostaining. A direct association was found between c-erbB3 and c-erbB4 mRNA and ER marker status measured by either RT-PCR (c-erbB3 P = 0.0003; c-erbB4 P = 0.02) or ICA (c-erbB-3 P = 0.002; c-erbB4 P = 0.01). Inverse associations were seen between c-erbB3 and c-erbB4 mRNA marker status and EGFR membrane protein (c-erbB3: P = 0.003; cerbB4: P = 0.003) and mRNA (c-erbB4: P = 0.009) status. These associations were reinforced by Spearman Rank Correlation Tests. A significant relationship was seen between Ki67 and c-erbB4 mRNA status and level. Measurements of c-erbB3 protein levels in tumour samples removed from a further 89 patients of known response to endocrine therapy: (i) confirmed the relationship between c-erbB3 and ER and (ii) identified that patients whose ER positive tumours expressed high levels of c-erbB3 were most likely to benefit from endocrine measures. A non-significant trend was recorded between c-erbB3 levels and Ki67 immunostaining. These results clearly demonstrate that increased c-erbB3 and c-erbB4 expression appears to be associated with the prognostically-favourable ER phenotype.
...
PMID:c-erbB3 and c-erbB4 expression is a feature of the endocrine responsive phenotype in clinical breast cancer. 978 38


1 2 3 Next >>

---