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)

Cultures of mural granulosa cells (mGCs) and cumulus oocyte complexes (COCs) were employed to investigate various aspects of follicle cell function and response to gonadotropins. Yet, such studies do not reveal the intricate cell-to-cell interactions in the whole follicle. Here we compare the ovulatory responses to LH/hCG or epiregulin (ER) of rat preovulatory follicles and of mGC and COC whether they were stimulated within the follicle or in primary cell cultures. The expression of TSG-6 and COX-2 mRNA varied according to the culture system and mode of stimulation. In primary cultures stimulated with LH or ER resulted in their lower expression as compared to stimulation of follicles. LH/hCG stimulated higher follicular and mGC AR, ER and EGFR mRNA levels than in primary mGC cultures. COCs stimulated by LH/hCG in vivo responded with AR, ER and EGFR mRNA expression, but not in culture where only EGFR mRNA was stimulated. The differences in gene expression of mGCs and COCs when stimulated within their intact follicle or in primary cultures revealed here underscore the important role of cell-cell interactions in follicle physiology. Therefore, results obtained in primary mGC cultures need careful validation in models reproducing such in situ interactions for revealing mGC activity within the intact follicle.
...
PMID:Response of follicle cells to ovulatory stimuli within the follicle and in primary culture. 1809 9

Among the targeted therapies used in the treatment of metastatic colorectal cancer (CRC), cetuximab was registered in France in 2004. This chimeric antibody inhibiting the Epidermal Growth receptor (EGFR) has been demonstrated to be efficient in the treatment of irinotecan-resistant metastatic CRC expressing the EGFR. Panitumumab, a fully humanized anti-EGFR antibody should soon be registered after failure of conventional chemotherapies. However, these costly and potentially toxic treatments are efficient in a little proportion of patients. It is so necessary to identify some factors able to better define whose patients will benefit from these treatments. The major potential predictive factors of response to cetuximab and/or panitumumab that have been evaluated in the literature, which are summarized in this review, are molecular factors involved more or less directly in the EGF signaling pathway. Among them, KRAS mutations, EGFR gene copy number and, more recently, epiregulin and amphiregulin expression are those, along with skin toxicity, which appear to be the most relevant and which will have to be evaluated in future clinical trials to be validated before being incorporated in therapeutic strategy of CRC.
...
PMID:[Predictive factors of response to anti-EGFR treatments in colorectal cancer]. 1823 May 79

We examined the expression of epiregulin and amphiregulin mRNA in 39 oral SCCs, 2 epithelial dysplasias and 7 normal gingivae by real-time RT-PCR. The mean expression level of epiregulin mRNA was higher in oral SCCs (0.29+/-0.50) than normal gingivae (0.01+/-0.007) and epithelial dysplasias (0.01+/-0.001). The expression level of epiregulin mRNA was significantly higher in oral SCCs than normal gingivae (Mann-Whitney U test, P=0.023). Epiregulin mRNA was higher in stage III/IV than in stage I/II oral SCCs. However, a significant association was not found. The mean expression level of amphiregulin mRNA was higher in oral SCCs (0.18+/-0.24) than normal gingivae (0.002+/-0.003) and epithelial dysplasias (0.01+/-0.001). Amphiregulin mRNA was significantly higher in oral SCCs than normal gingivae (Mann-Whitney U test, P=0.001). We then examined the expression of four EGF receptor mRNA in oral SCCs. The expression levels of HER1, HER2, HER3 and HER4 mRNA in oral oral SCCs were increased compared to those in normal gingivae. A significant correlation was found between the mRNA expression levels of epiregulin and HER2, HER3 and HER4 (Spearman's correlation coefficient by rank test, P=0.031, P=0.004 and P=0.027, respectively). Patients with oral SCC that have a high expression of epiregulin had a significantly shorter survival than those with low a expression (log-rank test, P<0.05). These results indicate that human epiregulin is closely linked to the increased or abnormal cell proliferation in human oral SCC.
...
PMID:Expression of epiregulin, a novel epidermal growth factor ligand associated with prognosis in human oral squamous cell carcinomas. 1849 65

Cancer-related mortality is caused in a large part by the metastasis of primary tumor. Each cancer has a particular way of spreading cancerous cells. Recently, genetic and pharmacological analysis identified the set of genes, such as epidermal growth factor receptor ligand epiregulin (EREG), cyclooxygenase-2 (COX2) and matrix metalloproteinases 1 and 2 (MMP-1 and MMP-2) that have been found to be associated with metastasis of breast cancer to lung. Inhibition of EGFR and COX2 could minimize lung metastasis of breast cancer in a clinical setting. In this review, we summarized the current knowledge on EREG, COX2, MMP-1 and MMP-2 in tumor development and metastasis.
...
PMID:Genes controlling spread of breast cancer to lung "gang of 4". 1856 69

Epiregulin belongs to the epidermal growth factor family, binds to the epidermal growth factor receptor, and its expression is upregulated in various cancer cells, but the regulatory mechanism is unclear. We investigated the regulatory mechanism of epiregulin expression in Ki-ras-transformed cancer cells. In 267B1/Ki-ras cells, the RAF/MEK/ERK pathway was constitutively activated, epiregulin was up-regulated, and the expression and phosphorylation of Ets-1 were augmented. The inhibition of ERK by PD98059 decreased epiregulin and Ets-1 expression and suppressed the growth of 267B1/Ki-ras cells. A chromatin immunoprecipitation assay demonstrated that Ets-1 was bound to human epiregulin promoter, and this binding was abolished by PD98059. Silencing of Ets-1 by RNA interference decreased cellular epiregulin transcript expression. We suggest that the Ki-ras mutation in 267B1 prostate cells constitutively activates the RAF/MEK/ERK pathway and induces the activation of the Ets-1 transcription factor, ultimately leading to the increased expression of epiregulin.
...
PMID:Epiregulin expression by Ets-1 and ERK signaling pathway in Ki-ras-transformed cells. 1894 81

The mutated K-ras gene is involved in approximately 30% of human cancers. In order to search for K-ras oncogene-induced modulators in lung tissues of K-ras transgenic mice, we performed microarray and proteomics (LC/ESI-MS/MS) analysis. Genes (RAB27b RAS family, IL-1RA, IL-33, chemokine ligand 6, epiregulin, EGF-like domain and cathepsin) related to cancer development (Wnt signaling pathway) and inflammation (chemokine/cytokine signaling pathway, Toll receptor signaling) were up-regulated while genes (troponin, tropomodulin 2, endothelial lipase, FGFR4, integrin alpha8 and adenylate cyclase 8) related to the tumor suppression such as p53 pathway, TGF-beta signaling pathway and cadherin signaling pathway were down-regulated by K-ras oncogene. Proteomics approach revealed that up-regulated proteins in lung adenomas of K-ras mice were classified as follows: proteins related to the metabolism/catabolism (increased from 7 to 22% by K-ras gene), proteins related to translation/transcription and nucleotide (from 4 to 6%), proteins related to signal transduction (from 3 to 5%), proteins related to phosphorylation (from 1 to 2%). ATP synthase, Ras oncogene family, cytochrome c oxidase, flavoprotein, TEF 1, adipoprotein A-1 BP, glutathione oxidase, fatty acid BP 4, diaphorase 1, MAPK4 and transgelin were up-regulated by K-ras oncogene. However, integrin alpha1, Ras-interacting protein (Rain), endothelin-converting enzyme-1d and splicing factor 3b were down-regulated. These studies suggest that genes related to cancer development and inflammation were up-regulated while genes related to the tumor suppression were down-regulated by K-ras, resulting in the tumor growth. Putative biomarkers such as cell cycle related genes (Cdc37), cancer cell adhesion (Glycam 1, integrin alpha8, integrin alphaX and Clec4n), signal transduction (Tlr2, IL-33, and Ccbp2), migration (Ccr1, Ccl6, and diaphorase 1 (Cyb5r3) and cancer development (epiregulin) can be useful for diagnosis and as prognosis markers and some of the target molecules can be applied for prevention of cancer.
...
PMID:Profiling of transcripts and proteins modulated by K-ras oncogene in the lung tissues of K-ras transgenic mice by omics approaches. 1908 87

Smoking is an independent prognostic factor of lung adenocarcinoma. Benzo[a]pyrene (B[a]P) is one of the strongest carcinogens and it is present in both the environment and cigarette smoke. In this study, the effect of B[a]P on the proliferative activity of lung adenocarcinoma cells was investigated. A lung adenocarcinoma cell line, A549, was cultured with B[a]P for various periods, and its proliferative activity was examined by an MTS assay. To investigate the intracellular events related to the proliferative activity, the gene expression profile was investigated by a microarray analysis and a quantitative RT-PCR, and the protein expression and activation status of Akt, ERK 1/2 and the epidermal growth factor receptor (EGFR) were examined by a western blot analysis. Following the culture with B[a]P for 24 weeks, the serum-independent proliferative activity was increased. A microarray analysis revealed that a reversible upregulation of the EGFR and epiregulin genes was recognized in the B[a]P treated cells, in which the overexpression of the phosphorylated EGFR protein was also recognized. The EGFR tyrosine kinase inhibitor reduced the cellular proliferation and the level of phosphorylation of ERK1/2, which is a downstream signal of the EGFR, in the B[a]P-treated A549 cells. Moreover, the B[a]P treatment increased the mRNA expressions of the ligands for EGFR such as amphiregulin and epiregulin. B[a]P increases the proliferative potential of lung adenocarcinoma cells through the EGFR signaling pathway.
...
PMID:Benzo[a]pyrene promotes proliferation of human lung cancer cells by accelerating the epidermal growth factor receptor signaling pathway. 1918 43

The developmental competence of in vitro-matured (IVM) rhesus macaque cumulus oocyte complexes (COCs) is deficient compared with in vivo-matured (IVM) oocytes. To improve oocyte quality and subsequent embryo development following IVM, culture conditions must be optimized. A series of experiments was undertaken to determine the role of epidermal growth factor (EGF) during IVM of rhesus macaque COCs. The addition of Tyrphostin AG-1478 (a selective inhibitor of the EGF receptor EGFR) to the IVM medium yielded fewer oocytes maturing to metaphase II of meiosis II (MII), decreased cumulus expansion, and a lower percentage of embryos that developed to the blastocyst stage compared with untreated IVM controls, indicating that EGFR activation is important for IVM maturation in the rhesus macaque. However, the addition of recombinant human EGF (r-hEGF) to the IVM medium did not enhance outcome. The expression of mRNAs encoding the EGF-like factors amphiregulin, epiregulin, and betacellulin in cumulus cells indicates that these factors produced by cumulus cells may be responsible for maximal EGFR activation during oocyte maturation, precluding any further effect of exogenous r-hEGF. Additionally, these results illustrate the potential futility of exogenous supplementation of IVM medium without prior knowledge of pathway activity.
...
PMID:Role for cumulus cell-produced EGF-like ligands during primate oocyte maturation in vitro. 1927 91

CD133+ cells are hemangioblasts that have capacity to generate into both hematopoietic and endothelial cells (ECs). Hypoxia/normoxia has shown to be the regulator of the balance between stemness and differentiation. In this study we performed Agilent's whole human genome oligo microarray analysis and examined the differentiation potential of the bone-marrow-derived CD133+ cells after hypoxic/normoxic preconditioning of CD133+ cells. Results showed that there was no significant increase in erythroid colony forming unit (CFU-E) and CFU-granulocyte, erythrocyte, monocyte, and megakaryocyte formation with cells treated under hypoxia/normoxia. However, a significant increment of EC forming unit at 24 h (143.2 +/- 8.0%) compared to 0 h (100 +/- 11.4%) was observed in CFU-EC analysis. Reverse transcription-polymerase chain reaction and immunostaining analysis showed that the differentiated cells diminished hematopoietic stem cell surface markers and acquired the gene markers and functional phenotype of ECs. The transcriptome profile revealed a cluster of 232 downregulated and 498 upregulated genes in cells treated for 24 h under hypoxia. The upregulated genes include angiogenic genes, angiogenic growth factor genes, angiogenic cytokine and chemokine genes, as well as angiogenic-positive regulatory genes, including FGFBP1, PDGFB, CCL15, CXCL12, CXCL6, IL-6, PTN, EREG, ERBB2, EDG5, FGF3, FHF2, GDF15, JUN, L1CAM, NRG1, NGFR, and PDGFB. On the other hand, angiogenesis inhibitors and related genes, including IL12A, MLLT7, STAB1, and TIMP2, are downregulated. Taken together, hypoxic/normoxic preconditioning may lead to the differentiation of CD133+ cells toward endothelial lineage, which may improve the current clinical trial studies.
...
PMID:Hypoxic/normoxic preconditioning increases endothelial differentiation potential of human bone marrow CD133+ cells. 2007 89

Early growth response-1 (Egr-1) is overexpressed in human prostate tumors and contributes to cancer progression. On the other hand, mutation of p53 is associated with advanced prostate cancer, as well as with metastasis and hormone independence. This study shows that in prostate cell lines in culture, Egr-1 overexpression correlated with an alteration of p53 activity because of the expression of SV40 large T-antigen or because of a mutation in the TP53 gene. In cells containing altered p53 activity, Egr-1 expression was abolished by pharmacological inhibition or RNAi silencing of p53. Although forced expression of wild-type p53 was not sufficient to trigger Egr-1 transcription, four different mutants of p53 were shown to induce Egr-1. Direct binding of p53 to the EGR1 promoter could not be detected. Instead, Egr-1 transcription was driven by the ERK1/2 pathway, as it was abrogated by specific inhibitors of MEK. Egr-1 increased the transcription of HB-EGF (epidermal growth factor), amphiregulin and epiregulin, resulting in autocrine activation of the EGF receptor (EGFR) and downstream MEK/ERK cascade. Thus, mutant p53 initiates a feedback loop that involves ERK1/2-mediated transactivation of Egr-1, which in turn increases the secretion of EGFR ligands and stimulates the EGFR signaling pathway. Finally, p53 may further regulate this feedback loop by altering the level of EGFR expression.
...
PMID:Mutant p53 initiates a feedback loop that involves Egr-1/EGF receptor/ERK in prostate cancer cells. 2019 Aug 20


<< Previous 1 2 3 4 5 6 7 Next >>

---