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)

ErbB-2 and EGFR (epidermal growth factor receptor) are expressed in lung adenocarcinomas and associated with a poor prognosis. Immunocytochemical analysis revealed erbB-2 and EGFR coexperession as a characteristic feature of most lung adenocarcinomas, and at levels of receptor expression present in bronchial epithelial cells. In primary lung tumours and cell lines, erbB-2 detected using Western blot analysis demonstrated low-level phosphotyrosine staining of the 185 kDa band, as compared with breast cancer cell lines. A549 and A427 lung adenocarcinoma cells treated with neu differentiation factor (NDF) showed increased erbB-2 phosphotyrosine staining, but to a much lesser extent than breast cancer cells. The lung cells were examined for expression of the potential autocrine growth factors NDF and transforming growth factor alpha (TGF-alpha) by Northern blot analysis. Both NDF and TFG-alpha mRNA were abundantly expressed in the A549 cells. NDF mRNA was highest during active cell proliferation and decreased in confluent cells or after treatment with the growth-inhibitory steroid dexamethasone. Primary tumours and cell lines expressed EGFR, showing higher basal level phosphotyrosine staining than erbB-2. Treatment with NDF and EGF (epidermal growth factor) stimulated cell growth, and in A549 cells the presence of both factors provided an additive increase in cell growth. The growth stimulus that ligand-activated erbB-2 and EGFR provides to lung adenocarcinoma cells may establish a background of continued cell proliferation over which other critical transforming events may occur.
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PMID:Expression and activation of erbB-2 and epidermal growth factor receptor in lung adenocarcinomas. 759 67

Gene targeting was used to create a null allele at the epidermal growth factor receptor locus (Egfr). The phenotype was dependent on genetic background. EGFR deficiency on a CF-1 background resulted in peri-implantation death due to degeneration of the inner cell mass. On a 129/Sv background, homozygous mutants died at mid-gestation due to placental defects; on a CD-1 background, the mutants lived for up to 3 weeks and showed abnormalities in skin, kidney, brain, liver, and gastrointestinal tract. The multiple abnormalities associated with EGFR deficiency indicate that the receptor is involved in a wide range of cellular activities.
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PMID:Targeted disruption of mouse EGF receptor: effect of genetic background on mutant phenotype. 761 84

With diagnostic stereotactic biopsies in astrocytoma sometimes false results will be encountered. A false positive result is defined as a histological diagnosis which is afterwards proved to be untrue. Although this happens very seldom (1-2%) in characterizing the tumor type (e.g. astrocytoma versus lymphoma), there is a probability of undergrading in malignant astrocytomas due to regional heterogeneity in malignancy grade. The issue of 'sampling error' has been addressed by many authors. It was shown that undergrading in astrocytomas is a likely event in fibrillar astrocytomas that often show geographically distinct areas of well and poorly differentiated elements. In a recent study on histological grading versus genetic characterization of heterogeneous astrocytomas we published that low-grade areas within high-grade malignant astrocytomas have already the genetic features of high-grade malignancy. Therefore, particularly in stereotactic biopsies which contain relatively small samples of tumor tissue, this fact is of paramount importance. Undergrading may lead to withholding radiotherapy from the patient and to falsification of long-term survival results in series of so-called low-grade astrocytomas. We like to stress the importance of taking biopsies from different parts of the tumor, especially from parts with different density enhancement to contrast with CT scanning, and will discuss the technical advancements made in the genetic grading of astrocytomas. Particularly loss of heterozygosity of chromosome 10 and eventually amplification of the EGFR indicate a high grade of malignancy.
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PMID:Genetic versus histological grading in stereotactic biopsies. 762 52

Twenty-one invasive squamous-cell carcinomas (SCC) of the bladder from Schistosoma-hematobium-infected patients were examined immunohistochemically for the expression of p53, Rb, EGFR and c-erbB-2 proteins; and screened by single-strand conformation polymorphism and sequencing for mutations in the ras (H, N, K) codon hotspots (12, 13, 61) and p53 (exons 4-9) genes. Positive staining for p53, EGFR and c-erbB-2 was reported in 38, 67 and 28% of tumors respectively. Only one of the tumors, the only one that was poorly differentiated, displayed an absence of nuclear Rb staining. Ras alterations were detected in the H-ras gene in 3 tumors, 2 of which harbored a codon-13 (Gly-->Arg) and one a codon-12 (Gly-->Ser) point mutation. p53 mutations were recorded in 12 tumors (57%), 6 of which stained positively for p53. Four tumors had exon-7 mutations (codons 235, 241 and 249; one tumor had 2 exon-7 mutations). Eight tumors were mutated in exon 8 (codons 264, 271, 273, 285, 286, 288 and 294), 5 of which harbored multiple mutations. One tumor had an insertion/deletion event in exon 9. The frequency of detection of over-expression of EGFR and c-erbB-2 in bilharzial-bladder lesions is comparable to that reported in TCC, contrasting with the infrequent loss of Rb expression found in invasive lesions associated with schistosomiasis infection. However, the detection of multiple p53 mutations in these lesions is suggestive of the involvement of a carcinogenic agent with maintenance of preferential activation of the H-ras gene.
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PMID:Molecular events underlying schistosomiasis-related bladder cancer. 762 66

T-CAR1 is a human carcinoma cell line established from a brain metastasis. The tumour cells overexpress EGFR and contain an amplified EGFR gene. In vitro in the presence of 5% human serum the tumour cells grow as adherent cells in monolayer. Shortly after exposure to EGF a large number of tumour cells round up and detach, whereas some remain adherent. At the same time a redistribution of actin occurs. Cytochalazin B prevented this reaction, which indicates that actin is involved in the detachment of the tumour cells. The EGF-detached tumour cells however, did not differ from the tumour cells which remained adherent after EGF-exposure with regard to parameters such as growth in soft agar, growth response to EGF, tumour necrosis factor-alpha, interferon-gamma, and carmustin (BCNU), level of EGFR gene expression and EGFR gene amplification, S-phase fraction, and amount of DNA. It was speculated whether the EGF-induced cellular detachment in vitro could be correlated to metastatic potential in vivo or not. In order to address this issue, in vivo studies with subcutaneous T-CAR1 tumours in nude mice were performed. Administration of EGF resulted in growth stimulation in contrast to growth inhibition in vitro, whereas no effect of EGF on the metastatic potential was observed. Thus, the EGF-mediated tumour cell detachment seems to be restricted to in vitro conditions only.
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PMID:EGF-effects in vitro and in vivo on a carcinoma cell line rich in EGFR. 764 40

The expression of Cath-D c-erbB-2 and EGFR in breast cancer and its correlation of lymphatic metastases were studied in 277 cases by immunohistochemical technique. Positive staining of Cath-D was detected in 107 cases (38.62%), of which, 89 cases (83.17%) had documented metastasis in the lymph nodes. One hundred and seventy cases (61.38%) stained negative for Cath-D, of which 64 cases (37.64%) had detectable lymphatic metastases. There was a significant difference in the rate of the lymphatic metastases between the Cath-D positive and Cath-D negative groups (P < 0.0001). Fifty-six out of 107 Cath-D positive cases (52.34%) were c-erbB-2 positive as well. However, only 27 out of 170 Cath-D negative cases (15.88%) were c-erbB-2 positive. The positive rate of c-erbB-2 in Cath-D positive group was significantly different from that of Cath-D negative group (P < 0.0001). Among those 107 Cath-D positive cases, 49 cases (45.79%) were EGFR positive. Only 24 cases (14.12%) were EGFR positive among the 170 Cath-D negative cases. The positive rate of EGFR between these two groups was also significantly different (P < 0.0001). The results suggest that Cath-D status can be used as an indicator of the aggressiveness of the breast cancer. Breast cancer cases with a positive Cath-D staining are more likely to have lymphatic metastases and a poor prognosis. Therefore, alternative therapeutic strategies and close follow-ups are needed for these patients.
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PMID:[The expression of Cath-D, c-erbB-2 and EGFR in breast cancer and its correlation to lymphatic metastasis]. 765 92

The nuclear transcription factor Fos is inducible by both steroid hormones and peptide growth factors. It thus forms a potential point of interaction between steroid hormone- and growth factor-directed pathways and may be critical in the subversion of steroid hormone control in breast cancer. In this light, the present study has used immunocytochemistry to demonstrate in clinical primary breast cancer that Fos expression is indeed significantly associated with a failure to respond to endocrine therapy, with preliminary analysis revealing a survival advantage for those patients whose tumours lacked Fos. Sustained elevated levels of Fos expression were significantly associated with further factors, notably peptide growth factors and their receptors (e.g., EGFR, TGF alpha), as well as with the proliferation marker Ki-67, which have been linked previously to endocrine insensitivity in breast cancer. In contrast, there appeared to be a trend for Fos to be absent in those tumours expressing markers of endocrine responsiveness (e.g., oestrogen receptor [ER], and also ER-mediated markers i.e., PR, pS2 or bcl-2). Interestingly, many of these trends were maintained in ER+ patients, suggesting that Fos may be of importance in directing loss of endocrine sensitivity in ER+ disease.
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PMID:Immunocytochemical localization of Fos protein in human breast cancers and its relationship to a series of prognostic markers and response to endocrine therapy. 765 91

Ret is a receptor protein tyrosine kinase that has been implicated in the development of the enteric nervous, endocrine, and renal systems. Mutations associated with multiple endocrine neoplasia types 2A and 2B (MEN 2A and 2B) have been shown to activate the intrinsic kinase and transforming ability of ret (Santoro, M., Carlomagno, F., Romano, A., Bottaro, D. P., Dathan, N. A., Grieco, M., Fusco, A., Vecchio, G., Matoskova, B., Kraus, M. H., and Paolo DiFiore, P. (1995) Science 267, 381-383). Using the cytoplasmic domain of Ret as bait in a yeast two-hybrid screen of a mouse embryonic library, it was discovered that the src homology 2 (SH2) domain containing protein Grb10 bound Ret. Grb10 belongs to an emerging family of SH2 containing adapter proteins, the prototypical member being Grb7. Using glutathione S-transferase fusion proteins, it was demonstrated that the SH2 domain of Grb10 specifically interacted with Ret. Additionally, using an EGFR/Ret chimera, it was shown that Grb10 bound Ret in an activation dependent manner in vivo. This is the first description of a receptor protein tyrosine kinase that utilizes Grb10 as a signaling intermediate.
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PMID:The Ret receptor protein tyrosine kinase associates with the SH2-containing adapter protein Grb10. 766 56

Immunohistochemical stainings for EGFR, c-erbB-2, p53 and PCNA were performed on 36 and 30 cases of intramucosal and advanced carcinomas of large intestine. Positive rate was 58.3%, 41.6%, 58.3% and 60.6% for EGFR, c-erbB-2, p53 and PCNA in the intramucosal cases, and 66.7%, 50%, 66.7% and 72.6% in the advanced ones, respectively. Relationship between EGFR and c-drbB-2 was more significant in the advanced carcinomas than that in the intramucosal ones. It seemed likely that relationship between p53 and c-erbB-2 was more significant than that between p53 and EGFR. Positive rate of PCNA was of intimate relationship among that of EGFR, c-erbB-2 and p53, and the positive rate increased in the advanced carcinomas.
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PMID:[Immunohistochemical study of PCNA, EGFR, c-erbB-2 and p53 in carcinomas of large intestine]. 767 43

The Shc gene encodes three overlapping proteins which all contain a carboxy-terminal SH2 domain. Shc proteins are ubiquitously expressed and are downstream targets and effectors of activated tyrosine kinases (TK). We investigated tyrosine-phosphorylation of Shc proteins in normal and transformed cells. In tumor cells with known TK gene alterations Shc proteins were constitutively phosphorylated and complexed with the activated TK. No constitutive Shc phosphorylation was found in primary cell cultures and normal tissues. In 14 of 27 tumor cell lines with no reported TK alterations, Shc proteins were constitutively phosphorylated and formed stable complexes with novel tyrosine-phosphorylated polypeptides. Ten distinct Shc-associated phosphoproteins were identified with molecular weights ranging from 30 to 200 kDa. In a subset of carcinoma cell lines, phosphorylated Shc proteins complexed with a p175 phosphoprotein that was identified as the constitutively activated EGFR. In one glioblastoma cell line, a Shc-associated p190 was identified as the activated PDGFR. In 13 of 14 acute leukemia samples phosphorylated Shc proteins were constitutively complexed with a p140 phosphoprotein. Some of the Shc-associated phosphoproteins (EGFR, PDGFR, erbB-2, Met, bcr-abl, H4-ret) bound both the Shc- and Grb2-SH2 domains in vitro; others (p175; p70-p80) only the Shc-SH2 domain and yet others (p140) only the Grb2-SH3 domains. These results indicate that Shc proteins are common substrates of constitutively activated TKs and that the analysis of Shc phosphorylation allow the identification of tumors with constitutive TK activation.
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PMID:Constitutive phosphorylation of Shc proteins in human tumors. 767 49


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