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

Angiogenesis is essential for tumor growth and metastasis and depends on the production of angiogenic factors by host and/or tumor cells. The role of angiogenesis and angiogenic factor expression in intestinal- and diffuse-type gastric cancer are undefined. Archival specimens of 51 intestinal-type and 38 diffuse-type human gastric carcinomas were examined for tumor vessel counts, angiogenic factor expression, and the presence or absence of angiogenic factor receptors on tumor endothelium using antibodies against vascular endothelial growth factor (VEGF) and its receptors (KDR and flt-1), basic fibroblast growth factor (bFGF) and its receptors (bek and flg), and factor VIII (endothelial cells). Vessel count and VEGF and bFGF expression were higher in intestinal-type than in diffuse-type gastric cancers (P = 0.01, P < 0.001, and P < 0.001, respectively). Similarly, vessel count and VEGF expression were higher in patients with liver metastasis than in patients with peritoneal dissemination (P = 0.003 and P = 0.01, respectively). Vessel count correlated with VEGF expression and the presence of endothelial KDR in intestinal-type gastric cancer (P = 0.003 and P = 0.02, respectively) but not diffuse-type gastric cancer. Vessel count, VEGF expression, and presence of endothelial KDR increased with increasing stage of disease in intestinal-type gastric cancer but not diffuse-type gastric cancer. The expression of bFGF and its receptors did not correlate with vessel count in either cancer type. These findings suggest that the pattern of metastasis in intestinal-type gastric cancer is angiogenesis dependent. The correlation of VEGF expression and its endothelial receptor with vessel count and stage of disease suggests that VEGF is at least one of the factors responsible for the induction of angiogenesis in intestinal-type gastric cancer.
 ...
PMID:Significance of vessel count and vascular endothelial growth factor and its receptor (KDR) in intestinal-type gastric cancer. 981 16

The K-sam gene, originally isolated as an amplified gene from the stomach cancer cell line KATO-III, is characterized by its preferential amplification in the undifferentiated type (diffuse type) of stomach cancer and encodes one of the receptors for heparin-binding growth factors or fibroblast growth factors. The K-sam gene has been isolated by different methods and has been designated BEK, TK14, and Cek2. The receptor for keratinocyte growth factor was also found to be encoded by the same gene. To examine the expression of the K-sam protein in stomach cancer, polyclonal antibody pK1-2 was raised against the extracellular domain of the gene product. This antibody detected K-sam proteins by Western blot and flow cytometry analyses in stomach cancer cell lines KATO-III and HSC39, in which the K-sam gene is amplified and overexpressed. By immunohistochemical analysis, 20 of 38 cases of the undifferentiated type of advanced stomach cancer were K-sam positive, whereas none of 11 cases of the differentiated or intestinal type revealed K-sam staining. The K-sam product was observed predominantly in diffusely infiltrative lesions. In one autopsy case, the K-sam protein was detected only focally in the primary tumor, whereas markedly increased staining for the K-sam product was detected diffusely in the metastasized tumor in the lymph node and liver. These results suggest that K-sam overexpression is associated with the malignant phenotype of the undifferentiated type of stomach cancer, such as infiltrative growth and metastasis.
 ...
PMID:Immunohistochemical detection of K-sam protein in stomach cancer. 981 10

Gastric adenocarcinoma is a malignant tumor with a high incidence and a low survival rate. In order to identify genetic alterations associated with this tumor, we screened 23 gastric adenocarcinomas for recurrent chromosomal imbalances by using comparative genomic hybridization (CGH). The most common gains of chromosomal material were found on chromosome arms 20q (10 cases), 16p (7 cases), and 1q (4 cases) and on chromosome 11 (4 cases). Losses were observed on chromosome arms 4q, 5q, 9p, and 21q (3 cases each). Four tumors exhibited high-level amplifications localized on chromosome regions 2p23-p24, 7q31-q32, 8p21-p22, 10q25-q26, 11q13, 17q11-q21, and 20q. Based on the position of these amplifications, candidate (onco)genes were selected and subsequently tested by Southern blot analysis of the respective tumors. Of the seven tested candidates, MYCN, MET, WNT2, and ERBB2 were found to participate in the amplicons of the respective tumor samples. Of these four presumably activated oncogenes, two, MYCN and WNT2, were previously not assumed to play a pathogenic role in stomach cancer. Among the other regions of imbalance, gain of 20q seems particularly interesting, because it is found in almost half of the analyzed cases and is highly amplified. Our data allowed us to narrow the relevant region down to the commonly gained bands 20q12-q13.1. This and other imbalanced regions provide a basis for searching new putative oncogenes and tumor suppressor genes involved in the development or progression of gastric adenocarcinoma.
 ...
PMID:Mapping of chromosomal imbalances in gastric adenocarcinoma revealed amplified protooncogenes MYCN, MET, WNT2, and ERBB2. 982 3

Many molecular events have been reported as prognostic factors in gastric cancer. Amplifications of K-sam and c-met genes are often associated with poorly differentiated adenocarcinoma, while ERBB2 genes are amplified in well--differentiated adenocarcinomas of the stomach. Alterations of tumor suppressor regulators confer progression of gastric cancer. On the other hand, multi autocrine loops of growth factors/receptors in gastric cancer cells play a key role in the progression and metastasis of cancer cells. The overexpression of K-sam gene, occurs in 31.9% of gastric cancers, and the prognosis of patients with overexpression of K-sam gene is poorer than those without it. Multivariate analysis reveals that the overexpression of K-sam gene is an important factor for prognosis, lymphnode metastasis and the depth of tumor invasion of gastric carcinomas.
 ...
PMID:[New molecular prognostic markers in gastric carcinoma]. 983 2

Many studies have reported changes in the carbohydrate structure of serum glycoproteins in disease, but this information is often of limited value for understanding disease mechanisms because it is obtained with simple and/or indirect methodologies that determine only one structural feature. On the other hand, more detailed carbohydrate methodologies are time-consuming and require a lot of purified material. Using haptoglobin (Hp) as a model protein, a new procedure was devised that determined the oligosaccharide composition of very small amounts of Hp in a relatively short time. The Hp was purified by batch affinity-chromatography, oligosaccharides were removed with PNGase F, and the oligosaccharide composition of charged species was determined using HPAEC/PAD (Dionex carbohydrate analyser). The method was applied to the analysis of Hp from eight healthy individuals and 37 patients with different inflammatory diseases or cancers. Twenty-seven oligosaccharides were consistently detected, but the majority could not be identified. However, by calculating retention times relative to the sialylated biantennary peak (Neu5Ac(alpha)2-3/6Gal(beta)1-4GlcNAc(beta)1-2Man(alpha)1-6(Neu 5Ac(alpha)2-3/6Gal(beta)1-4GlcNAc(beta)1-2Man(alpha)1-3)Man(beta)1-4G lcNAc(beta)1-4GlcNAc) it was possible to compare profiles quantitatively. Although no peak was identified as disease-specific, characteristic and reproducible profiles were obtained. Particularly striking were reductions in the major peaks in Crohn's disease, rheumatoid arthritis, stomach cancer, accompanied by increases in unidentified peaks. Previous studies suggested that many of the unknown peaks were due to increased sialylation and fucosylation. Only small changes in patterns were observed for breast and ovarian cancer. The new procedure will be very useful in the characterization of oligosaccharide composition of glycoproteins in clinical specimens.
 ...
PMID:Reproducible and sensitive determination of charged oligosaccharides from haptoglobin by PNGase F digestion and HPAEC/PAD analysis: glycan composition varies with disease. 988 48

Our recent studies using comparative genomic hybridization showed that gain or amplification at the 17q12-q21 region is very common in the intestinal type of gastric cancer. Here, we describe a fluorescence in situ hybridization study with gastrin (GAS)-specific and ERBB2-specific probes on ten specimens of gastric carcinoma that, by using comparative genomic hybridization, showed 1) DNA copy number gain or amplification at 17q12-q21, a region known to harbor the GAS and ERBB2 genes (four cases); 2) gain of the entire chromosome 17 (three cases); or 3) normal copy number of chromosome 17 (three cases). GAS and ERBB2 protein expression was studied by Western immunoblotting from gastric cancer cell lines with or without gain at 17q12-q21 as well as a breast cancer cell line with ERBB2 amplification. Our results showed that simultaneous amplification of both GAS and ERBB2 was four- to ninefold in the tumors with the 17q12-q21 amplification. Both genes were amplified in the same nuclei, and the hybridization signals were localized to the same region of the nucleus. Overexpression of GAS and ERBB2 was observed by Western immunoblotting only in the gastric cancer cell line with gain at 17q12-q21. The ERBB2 amplification is also a recurrent change in breast cancer. To investigate whether the GAS amplification is unique in gastric cancer, fluorescence in situ hybridization analysis was performed on 40 breast cancer cell lines. The ERBB2 amplification was observed in 11 cell lines, but none of the lines showed the GAS amplification. This indicates that the formation of an amplicon, in which both the GAS and the ERBB2 genes are amplified, might be unique in gastric cancer, especially in its intestinal type, and that simultaneous amplification of both genes is important to the tumorigenesis of intestinal gastric cancer. We demonstrate here for the first time that a gene of a physiological hormone is amplified in tumors that originate from cells that normally secrete the hormone.
 ...
PMID:Concomitant gastrin and ERBB2 gene amplifications at 17q12-q21 in the intestinal type of gastric cancer. 989 5

The presence of RON and its variant isoform in malignant and non-malignant human colonic tissues was examined by immunohistochemistry using paraffin-embedded sections and RT-PCR analysis followed by direct sequencing of PCR product using RNAs isolated from frozen tissues. In normal colonic mucosa, RON was uniformly expressed in crypt cells, especially in the bottom of crypta. On the other hand, the expression was distributed heterogeneously in adenomas and in colon cancer. The expression of RON was significantly related to the degree of differentiation of colon cancer and the deletion of the expression was observed in colon cancer specimens with high incidence. The RT-PCR analysis of RNA isolated from non-malignant and malignant colonic tissue revealed the presence of two RON mRNA isoforms with 432-bp and 286-bp. Direct sequencing of major product of 432-bp was revealed to be identical to that of human wild-type RON. On the other hand, major product of 286-bp was revealed to be almost identical to that of a splicing variant of RON transcript which has been found in human gastric cancer cell line, KATO-III. The results obtained in this study may indicate that both wild-type RON and its variant isoform play an important role in regulating the normal function of colonic mucosa such as differentiation and motile activity and the expression of both wild-type RON and its variant isoform could be considered to be reduced during malignancy of human colonic mucosa.
 ...
PMID:Presence of RON receptor tyrosine kinase and its splicing variant in malignant and non-malignant human colonic mucosa. 1049 52

Activation of peroxisome proliferator-activated receptor gamma (PPARgamma) is shown to inhibit the growth of MKN-45 cells, a human gastric cancer cell line, which overexpresses c-Met tyrosine kinase. The aim of the present study was to investigate whether PPARgamma regulates the expression of c-Met. Two days after the activation of PPARgamma by troglitazone, a potent and selective PPARgamma ligand, a dramatic reduction of c-MET transcripts and the c-Met protein in MKN45 cells was observed. The luciferase assay showed that the activation of PPARgamma suppressed -249 to +330 c-MET promoter activity, driven by cotransfection of ETS-1 expression vector. These data demonstrate that PPARgamma activation is capable of suppressing Ets-induced c-MET gene transcription. Thus, it is possible that the growth inhibitory effect of PPARgamma on MKN-45 cells is related to the suppression of c-MET transcription.
 ...
PMID:PPARgamma inhibits the expression of c-MET in human gastric cancer cells through the suppression of Ets. 1055 88

Liver cancer and gastric cancer are the most common solid tumors worldwide. Transforming growth factor-beta (TGF-beta) production and lack of response to TGF-beta growth inhibitory effects have been associated with tumor progression and therapeutic resistance. HepG2, Hep3B, and SK-HEP-1 human liver cancer lines produce 3, 5.7, and 2.5 ng TGF-beta1; 1.4, 2, and 4 ng TGF-beta2 and 0.15, 0.2 and 0.22 ng TGF-beta3 per 107 cells (24 h). Expression of the TGF-beta type I receptor is 20x, 1x, and 0.6x the level in mink lung MvLu1 cells in the HepG2, Hep3B, and SK-HEP-1 cells, respectively. HepG2 and Hep3B cells do not express the TGF-beta type II receptor while SK-HEP-1 cells express 7x the level found in mink lung MvLu1 cells. Hs 746T, KATO III, RF-1, and RF-48 human gastric cancer cell lines produce 12. 5, 0.35, 0.4, and 0.4 ng TGF-beta1; 2.6, 0.95, 0.5, and 0.52 ng TGF-beta2 and 0.42, 0.17, 0.12, and 0.14 ng TGF-beta3 per 107 cells (24 h). Expression of TGF-beta type I receptor is 0.7x, 0.7x, 0.8x, 0.6x the level in mink lung MvLu1 cells in the Hs 746T, KATO III, RF-1 and RF-48 cells, respectively. KATO III cells are lacking in the TGF-beta type II receptor while Hs 746T, RF-1 and RF-48 cells express 10x, 0.8x, and 1x the levels in mink lung MvLu1 cells. The IC50 for TGF-beta1 is >>10 ng/ml in all of these lines except RF-48 where TGF-beta1 is mitogenic. The response of the cell lines to radiation, doxorubicin, mitomycin C, cisplatin, 5-fluorouracil, methotrexate, and gemcitabine showed that SK-HEP-1 was the most drug resistant liver cancer cell line and KATO III was the most drug resistant gastric cancer cell line. Overall, there was no correlation between TGF-beta secretion in cell culture and sensitivity of the cells to anticancer agents. Increased TGF-beta1 levels were detectable in the plasma of nude mice bearing Hep3B and Hs 746T xenografts. Those tumors which secreted greater amounts of TGF-beta were more therapeutically resistant in vivo.
 ...
PMID:Transforming growth factor-beta and response to anticancer therapies in human liver and gastric tumors in vitro and in vivo. 1067 95

Hepatocyte growth factor (HGF) activator inhibitor type 1 (HAI-1) and type 2 (HAI-2) are new Kunitz-type serine protease inhibitors that were recently purified and cloned from the human stomach cancer cell line MKN45 as specific inhibitors against HGF activator. Both proteins contain two Kunitz inhibitor domains and are expressed abundantly throughout the gastrointestinal tract, in addition to the placenta, pancreas, and kidney. In this study, to assess the possible roles of HAI-1 and HAI-2 in the intestinal mucosa, we examined the expression of HAI-1 and HAI-2 during regeneration of the intestinal mucosa. Immunohistochemical studies revealed that HAI-1 but not HAI-2 was detected more strongly in regenerative epithelium than in normal epithelium, although both proteins were detected throughout the human gastrointestinal tract. During the course of acetic acid-induced experimental colitis in an in vivo mouse model, HAI-1 but not HAI-2 was upregulated in the recovery phase, suggesting that HAI-1 but not HAI-2 is associated with the regeneration of damaged colonic mucosa. Upregulation of HAI-1 may serve to downregulate the proliferative response after initial activation of MET receptor by HGF/scatter factor after an injury.
 ...
PMID:Upregulation of HGF activator inhibitor type 1 but not type 2 along with regeneration of intestinal mucosa. 1076 18


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