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

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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 expression of protein-tyrosine kinases (PTKs; ATP:protein-tyrosine O-phosphotransferase, EC 2.7.1.112) was studied in normal human lung and various tumors by PCR followed by molecular cloning and sequence analysis. Six known PTKs (YES, FGR, LYN, HCK, PDGFB-R, and CSF1-R), as well as two additional members of this enzyme family, were detected in lung. One of the newly discovered sequences appears to represent a group of cytosolic PTKs. The cDNA sequence of the second unknown PTK revealed that it is a fourth member of the fibroblast growth factor receptor family. It was therefore called TKF (tyrosine kinase related to fibroblast growth factor receptor). Among a wide variety of cells and tissues tested, including human lymphocytes and macrophages, TKF was only found expressed in lung. Apart from normal lung, TKF expression could be demonstrated in some tumors of lung origin, but also in malignancies not derived from lung tissues. As fibroblast growth factors are generally involved in a variety of functions such as mitogenesis, angiogenesis, and wound healing, the specific expression of a receptor-related gene in lung only may point to yet another special function of this group of proteins.
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PMID:Two additional protein-tyrosine kinases expressed in human lung: fourth member of the fibroblast growth factor receptor family and an intracellular protein-tyrosine kinase. 172 May 39

Oncogene dosage and expression were studied in 16 testicular neoplasms, 14 of germ cell and two of non-germ cell origin. In comparison with normal DNA, tumour DNA of a total of eight patients (seven with germ cell neoplasm and one with testicular lymphoma) showed increased dosages of KRAS2, PDGFA, EGFR, MET and PDGFB. The most frequent (occurring in six tumours) and prominent (up to 3-4-fold) increases were detected in the dosages of KRAS2 (on chromosome 12p) and PDGFA (chromosome 7p), relative to a reference locus from chromosome 2. Importantly, there was a similar increase in 12p dosage in general in these tumours, suggesting the presence of the characteristic isochromosome 12p marker. On the contrary, possible 7p polysomy (assessed by molecular methods) did not explain the PDGFA (or EGFR) changes in all cases. NRAS, MYCN, CSFIR, MYB, MYC, ABL, HRASI, TP53, and ERBB2 did not reveal any consistent alterations in tumour DNA. In RNA dot blot assays the expression of KRAS2, PDGFA, EGFR, or MYC was generally not increased in the tumour samples when compared to that in normal testicular tissue of the same patients although there was interindividual variation in mRNA levels. It thus appears that while oncogene dosage changes occur in a proportion of testis cancers, they are often part of changes in large chromosomal regions or whole arms and are seldom accompanied by altered expression.
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PMID:Oncogenes in human testicular cancer: DNA and RNA studies. 182 52

The gene for the human platelet-derived growth factor (PDGF) A type receptor was assigned to the proximal long arm of chromosome 4 by using in situ hybridization. Of 141 labeled metaphase cells, 74 had grains over chromosome 4, with a distinct peak at bands q11-q12. The presence of the gene on chromosome 4 was also confirmed by hybridization to chromosome specific libraries. This places the PDGFA receptor gene in the same region of chromosome 4 as the KIT oncogene, another member of the PDGF growth factor receptor subfamily. The two other members of this gene family, the PDGFB receptor and the colony stimulating factor-1 (CSF1) receptor, are closely linked on the distal half of the long arm of chromosome 5.
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PMID:Human PDGFA receptor gene maps to the same region on chromosome 4 as the KIT oncogene. 256 17

PDGFs and their receptors expression were examined in a series of 46 meningiomas by using specific monoclonal antibodies. The immunostaining was quantified by an image analyser and the results correlated with clinical and morphological data (histological type and grade). In addition, since the PDGFB chain is encoded by the c-sis proto-oncogene localized on chromosome 22 and because monosomy 22 has been frequently reported in meningiomas, PDGFs and PDGFRs expression have been correlated with cytogenetic analysis performed in 29 cases. The results demonstrate PDGF A and PDGF B expression in most meningioma specimens and co-expression of these growth factors in numerous cells. PDGF A and B immunoreactivity was related to histological grade. PDGFR beta expression was strong in almost all meningiomas whereas PDGFR alpha was low. PDGFR alpha expression was related to tumour location and grade and PDGFR beta to histological subtype only. The cytogenetic analysis was not related to PDGFB chain expression. Taken together these data further confirm PDGF and PDGFR expression in human meningioma; PDGF may exist as an heterodimer (AB) as well as its receptor. The lack of correlation between cytogenetic analysis and PDGF values, the low level of PDGFB in recurrent meningiomas suggests that it is unlikely that the c-sis proto-oncogene plays an important role in the genesis of meningiomas.
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PMID:Platelet-derived growth factor (PDGF) and receptor (PDGFR) expression in human meningiomas: correlations with clinicopathological features and cytogenetic analysis. 753 Dec 97

Over a 3 year period, 19 surgically resected giant cell tumors of bone and cell lines from 4 cases were analysed cytogenetically. The results indicate that most of the tumor cells are heteroploid, the chromosome model number is predominantly hypodiploid. Karyotypic analysis demonstrated that the loss of chromosome #17, #18 appears more frequently (with a loss rate of 60% and 45% respectively), terminal deletion and telomeric fusion were the most common cytogenetic aberrations. We compared highly nonrandom tumor cell chromosome breakpoints and the same patient's somatic cell chromosome fragile sites with published oncogenes and found that 7q32, 13q13, 22q12 were coincident with MET, FLT, YES2/PDGFB (sis) respectively. Whether these loci abnormalities correlate with tumorgenesis needs further investigation.
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PMID:[Cytogenetic analyses on giant cell tumor of bone]. 795 56

In this study, we detected the expression of platelet-derived growth factor (PDGF) and its receptor in 61 human meningiomas by immunohistochemistry and in situ hybridisation. The results showed that almost all the 61 meningiomas expressed PDGFBB and PDGF beta receptor and the positive rate of PDGFAA was 49%. Only two meningiomas expressed PDGF alpha receptor. The positive rate and the immunostaining intensity of PDGFBB and PDGF beta receptor were higher in atypical meningiomas than in benign types. There was no significant difference between the different types of benign meningiomas. The expression of PDGFB chain mRNA was coincident with that of PDGFB chain protein. There was no correlation between the expression of PDGFAA and the types or grades of meningiomas. The correlation between overexpression of PDGFBB/R beta and tumour grade provides a useful parameter in evaluating the prognosis of patients with meningiomas. The proliferative activity of meningiomas was evaluated by the proliferating cell nuclear antigen labelling index (PCNA LI). In the 61 meningiomas, the average PCNA LI (%) was 1.8+/-1.3, 1.9+/-1.3, 1.7+/-0.8 and 11.6+/-5.3 (in fibrous, meningothelial, transitional and atypical meningiomas, respectively). Statistic analysis shows that the PCNA LI is higher in atypical meningiomas than that in benign types, and there was no significant difference between the different types of benign meningiomas. The expression of PDGFBB and PDGF beta receptor was significant enhanced in ascending order from low PCNA LI meningiomas to high ones. This result suggested that PDGFBB/R beta autocrine loop may stimulate the growth of meningiomas. In this study, we also detected the cell apoptosis of meningiomas by terminal deoxynucleotidyl transferase mediated dUTP nick end labelling (TUNEL) method. The average apoptosis labelling index (%) was 0.11+/-0.05, 0.08+/-0.04, 0.09+/-0.03 and 0.35+/-0.15 in fibrous, meningothelial, transitional and atypical meningiomas respectively. The apoptosis labelling index was higher in atypical meningiomas than that in benign types. There was a positive correlation between the apoptosis labelling index and PC NA LI of meningioma. When the positive rate of PDGFBB and/or PDGF beta receptor was higher in meningioma, the apoptotic cells was also increased. In conclusion, the overexpression of PDGFBB and its relevant receptor PDGFR beta in meningiomas was correlated with grade of meningiomas and the proliferative activity of meningiomas; PDGFBB/R beta autocrine loop may play an critical role in the pathogenesis of meningiomas.
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PMID:Expression of PDGF and its receptor as well as their relationship to proliferating activity and apoptosis of meningiomas in human meningiomas. 1138 26

To investigate genetic alterations in primary cutaneous B-cell lymphomas (PCBCLs), we have analyzed 29 cases of PCBCL. Comparative genomic hybridization showed chromosome imbalances (CIs) in 12 cases (41%). The mean number of CIs per sample was 2.05 +/- 2.97, with gains (1.48 +/- 2.38) more frequent than losses (0.56 +/- 1.40). The common regions of gains were 18/18q (50%), 7/7p (42%), 3/3q (33%), 20 (33%), 1p (25%), 12/12q (25%), and 13/13q (25%), whereas loss of 6q was frequent (42%). Among the different subsets of PCBCLs, CI was seen in 50% of diffuse large-cell lymphomas (DLCLs), 33% of marginal zone lymphomas, and 8% of follicle center cell lymphomas and unclassified lymphomas. A similar pattern of CI was observed in these lymphomas, but loss of 6q and gains of 3/3q were present only in DLCLs. Microarray-based genomic analysis of four DLCL cases identified oncogene gains of SAS/CDK4 (12q13.3) in three cases and MYCL1 (1p34.3), MYC (8q24), FGFR2 (10q26), BCL2 (18q21.3), CSE1L (20q13), and PDGFB (22q12-13) in two cases, whereas losses of AKT1 (14q32.3), IGFR1 (15q25-26), and JUNB (19p13.2) were identified in three cases, and losses of FGR (1p36), ESR (6q25.1), ABL1 (9q34.1), TOP2A (17q21-22), ERBB2 (17q21.2), CCNE1 (19q13.1), and BCR (22q11) were each identified in two cases. In addition, real-time-polymerase chain reaction detected amplification of BCL2 in 5 of 29 cases. These findings suggest that there are complex but consistent genetic alterations associated with the pathogenesis of PCBCLs.
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PMID:Comparative genomic hybridization analysis of primary cutaneous B-cell lymphomas: identification of common genomic alterations in disease pathogenesis. 1220 78

Hybridization with cDNA arrays was used to obtain expression profiles of 263 protein-tyrosine kinase (PTK), protein-tyrosine phosphatase (PTP), dual-specific phosphatase (DuSP), and other genes for the normal prostate tissue, primary prostate carcinomas (PC) of 84 patients, 7 xenografts, and 5 carcinoma cell lines. Analysis of 96 profiles revealed eight clusters of genes coexpressed in PC (coefficient of correlation r > 0.7). According to the known functions of their genes, the clusters were designated as proliferating-cell (CDC42, TOP2A, FGFR3, MYC, etc.), neoangiogenesis and blood-cell (LCK, VAV1, KDR, VEGF, MMP9, SYK, PTPRS, and FLT4), invasion-1 and invasion-2 (ADAM17, TRPM2, DUSP6, VIM, CAV1, CAV2, JAK1, PTPNS1, FYN, and PDGFB), HER2, and PSA/PSM/HER3. Basing on expression profiles of 66 genes, a molecular classification of PC was constructed and allowed discrimination between PC and cell lines or xenografts at 98.9% probability. The results suggested that, along with PSA, PSM (FOLH1), kallikrein-2, and a-2-macroglobulin, cell signaling genes EGFR, HER2, HER3, TOP2, KRT8, KRT18, VEGF, CD44, VIM, CAV1, and CAV2 may serve as diagnostic and prognostic markers in PC. The HER2, VEGF, and CD44 genes and the MMP and ADAM families were assumed to be promising targets for inhibitors of PC cell proliferation and metastasis.
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PMID:[Gene expression profiles of protein kinases and phosphatases obtained by hybridization with cDNA arrays: molecular portrait of human prostate carcinoma]. 1262 52

We studied a female patient initially diagnosed with Costello syndrome who carries an apparently balanced translocation, t(1;22) (q24.3;q13.1). Molecular characterization of the translocation revealed a mosaic of two derivative chromosomes 1 in her peripheral blood lymphocytes, in one of which the coding region of the platelet-derived growth factor (PDGFB; chromosome 22q13.1) gene was disrupted. Both the initial translocation and the secondary intrachromosomal rearrangement appear to have occurred by nonhomologous (illegitimate) recombination. In 18 patients with Costello syndrome, mutation analysis of the genes belonging to the PDGF/R family, PDGFA, PDGFB, PDGFC, PDGFD, PDGFRA, and PDGFRB, revealed no pathogenic mutations. Reevaluation of the clinical symptoms of the translocation patient challenges the diagnosis of Costello syndrome in this patient. In total RNA isolated from lymphocytes of the translocation patient, we identified four different fusion transcripts consisting of PDGFB exons and parts of chromosome 1q24.3. In two of the mRNAs, exon 6 of PDGFB, encoding the 41 C-terminal amino acid residues, was absent. Immunofluorescence analysis showed that the wild-type protein was dispersed and formed a network-like structure in the extracellular matrix, whereas the two aberrant PDGFB proteins were localized in aggregates. We speculate that the biological consequences of the mutant PDGFB allele contributed to the unique disease phenotype of the translocation patient.
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PMID:Disruption of the PDGFB gene in a 1;22 translocation patient does not cause Costello syndrome. 1508 Nov 17

Array-based comparative genomic hybridization (aCGH) allows the identification of DNA sequence copy number changes at high resolution by co-hybridizing differentially labelled test and control DNAs to a micro-array of genomic clones. The present study has analysed a series of 23 formalin-fixed, paraffin wax-embedded tissue samples of Barrett's adenocarcinoma (BCA, n = 18) and non-neoplastic squamous oesophageal (n = 2) and gastric cardia mucosa (n = 3) by aCGH. The micro-arrays used contained 287 genomic targets covering oncogenes, tumour suppressor genes, and DNA sequences localized within chromosomal regions previously reported to be altered in BCA. DNA sequence copy number changes for a panel of approximately 50 genes were identified, most of which have not been previously described in BCA. DNA sequence copy number gains (mean 41 +/- 25/BCA) were more frequent than DNA sequence copy number losses (mean 20 +/- 15/BCA). The highest frequencies for DNA sequence copy number gains were detected for SNRPN (61%); GNLY (44%); NME1 (44%); DDX15, ABCB1 (MDR), ATM, LAMA3, MYBL2, ZNF217, and TNFRSF6B (39% each); and MSH2, TERC, SERPINE1, AFM137XA11, IGF1R, and PTPN1 (33% each). DNA sequence copy number losses were identified for PDGFB (44%); D17S125 (39%); AKT3 (28%); and RASSFI, FHIT, CDKN2A (p16), and SAS (CDK4) (28% each). In all non-neoplastic tissue samples of squamous oesophageal and gastric cardia mucosa, the measured mean ratios were 1.00 (squamous oesophageal mucosa) or 1.01 (gastric mucosa), indicating that no DNA sequence copy number chances were present. For validation, the DNA sequence copy number changes of selected clones (SNRPN, CMYC, HER2, ZNF217) detected by aCGH were confirmed by fluorescence in situ hybridization (FISH). These data show the sensitivity of aCGH for the identification of DNA sequence copy number changes at high resolution in BCA. The newly identified genes may include so far unknown biomarkers in BCA and are therefore a starting point for further studies elucidating their possible role in Barrett's carcinogenesis.
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PMID:Array-based comparative genomic hybridization for the detection of DNA sequence copy number changes in Barrett's adenocarcinoma. 1522 37


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