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)

By somatic cell fusion studies between noninvasive mouse T-lymphoma cells and invasive human activated normal T-cells we have previously shown that the genetic information responsible for the induction of invasive and metastatic potential in interspecies T-cell hybrids is located on human chromosome 7. Apparently, genes derived from normal activated T-cells are dominantly expressed in the hybrids and control the invasive and, as a consequence, metastatic potential of these T-lymphoma cells. To sublocalize the invasion-inducing locus on chromosome 7 we have generated hybrids that harbor only specific regions of human chromosome 7 with or without a small fragment of human chromosome 21. Analysis of these hybrids revealed that the invasion-inducing locus maps to 7p12----cen. The human DNA complement of the hybrids was confirmed by Southern blot analysis using a large panel of chromosome 7-specific DNA probes. Several of these genes could be further sublocalized. These included: ARAF2 to 7p12----cen, D7S21 to 7pter----p12, ACTB to 7p15----p12, EGFR to 7p12, MDH2 to 7cen----q22, and PDGFA to 7pter----p15.
...
PMID:Sublocalization of an invasion-inducing locus and other genes on human chromosome 7. 150 15

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.
...
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.
...
PMID:Human PDGFA receptor gene maps to the same region on chromosome 4 as the KIT oncogene. 256 17

The molecular events leading to the development and progression of serous ovarian carcinoma are not completely understood. We performed a large scale survey for the identification of differentially expressed genes in serous ovarian carcinoma by using cDNA array analysis. Differences in gene expression between serous adenocarcinoma and benign serous adenoma, and between advanced and/or moderately or poorly differentiated and local, highly differentiated serous adenocarcinoma were assessed. The most striking difference between adenocarcinoma and benign adenoma was upregulation of RHOGDI2 in the carcinomas irrespective of the clinical tumor stage. Other changes in carcinoma were upregulation of MET and Ne-dlg, and downregulation of HGFAC, desmin, and PDGFA. The most prominent differences between advanced and local adenocarcinoma were upregulation of COL3A1, CFGR, and MET in advanced carcinoma, and downregulation of HGFAC, FZD3, and BFL1 in the same tumors. In conclusion, significant differences were found in the gene expression between benign and malignant serous ovarian tumors, and between local, highly differentiated and advanced and/or moderately or poorly differentiated serous adenocarcinomas. The differentially expressed genes may be related to the carcinogenesis and progression of the malignant growth.
...
PMID:Changes in gene expression during progression of ovarian carcinoma. 1145 21

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.
...
PMID:Disruption of the PDGFB gene in a 1;22 translocation patient does not cause Costello syndrome. 1508 Nov 17

Endomyocardial fibrosis (Loeffler's endocarditis) is the main cause of poor outcome in Hyper Eosinophilic Syndrome (HES) and Eosinophilic Leukemia (EL). Reversion of the cardiac damage has been seldom reported, and thrombi can superimpose on infiltrated walls, originating oembolic complications. The tyrosine kynase inhibitor imatinib has been recently employed in patients affected by HES or EL, with impressive results. We have treated with imatinib a young patient affected by Loeffler's endocarditis during EL. Loeffler's endocarditis was studied by transthoracic Doppler echocardiography with and without the contrast agent SonoVue. Cytogenetics, FISH and molecular analysis showed the presence of the FIP1L1/PDGFRA fusion gene, recently detected in a majority of HES patients. Standard echocardiography revealed a large infiltration of the apical region, with apparently pedunculate corpora floating in the LV chamber; after SonoVue injection, a thick endo-myocardial infiltration involving papillary muscles and tendinous chords appeared, which simulated mobile thrombi at standard echography. Treatment with low dose imatinib caused rapid regression of both eosinophilic proliferation and endomyocardiopathy. The fusion gene FIP1L1-PDGFRA was found significantly decreased after a few months of treatment. Using a contrast echocardiographic approach, we demonstrated the non-thrombotic origin of the "in plus" image in our patient and its rapid resolution following imatinib treatment. Imatinib is an excellent candidate for first line treatment of Loeffler's endocarditis, especially when the FIP1L1/PDGFA fusion gene is detected.
...
PMID:Rapid reversion of Loeffler's endocarditis by imatinib in early stage clonal hypereosinophilic syndrome. 1562 68

Gliosarcomas are rare and poorly characterized malignant brain tumors that exhibit a biphasic tissue pattern with areas of gliomatous and sarcomatous differentiation. These tumors are histological variants of glioblastoma, displaying a similar genetic profile and dismal prognosis. Up-regulation of PDGFR subfamily of tyrosine kinase members, PDGFR-alpha and c-Kit, and their intracellular effectors RAS/RAF/MAPK has a crucial role in the cancer development. In addition, signal transduction mediated by activating mutations of c-Kit and PDGFR can be effectively blocked by specific tyrosine kinase inhibitors, such as Imatinib mesylate. The aim of this study was to characterize the molecular alterations of PDGFR signaling in gliosarcomas. Six cases were analyzed by immunohistochemistry for the expression of PDGFR-alpha, c-Kit and their ligands PDGF-A and SCF, respectively. The cases were further evaluated for the presence of activating mutations of PDGFR-alpha (exons 12 and 18) and c-kit (exons 9, 11, 13, and 17), as well as B-RAF (exons 11 and 15). Expression of PDGF-A was found in all cases and co-expression of PDGFR-alpha was observed in three cases. Four cases showed expression of SCF, and c-Kit was observed only in one case that also expressed SCF. Generally, immunoreaction predominates in the glial component. The mutational analysis of PDGFR-alpha showed the presence of an IVS17-50insT intronic insertion in two cases, one of them also with a 2472C > T silent mutation; this silent mutation was also found in another case. Glioma cell line analysis of IVS17-50insT insertion showed no influence on PDGFR-alpha gene splicing. No mutations were detected in c-kit and B-RAF oncogenes. Our results indicate that activating mutations of PDGFR-alpha, c-kit and B-RAF are absent in gliosarcomas. Nevertheless, the presence of a PDGFR-a/PDGFA and c-Kit/SCF autocrine/paracrine stimulation loop in a proportion of cases, supports the potential role of specific tyrosine kinase inhibitors in the treatment of gliosarcomas.
...
PMID:Molecular characterization of PDGFR-alpha/PDGF-A and c-KIT/SCF in gliosarcomas. 1637 64

Chondrosarcomas represent 20% of all primary bone sarcomas, and many studies have attempted to unravel molecular targets for future development of new therapies. The aim of this study was to investigate the expression/activation of PDGFRalpha, PDGFRbeta and KIT receptor tyrosine kinases (RTKs) as potential therapeutic targets in conventional central primary chondrosarcomas (CCS). The expression of PDGFRalpha, PDGFRbeta and KIT RTKs was detected in 16 CCSs using immunohistochemistry (IHC), and their level of expression and activation status were analysed by immunoprecipitation and western blot experiments. PDGFRalpha, PDGFRbeta and KIT cDNAs were screened to verify the presence of activating mutations and the presence of the cognate ligands was analysed by means of RT-PCR. RTK gene amplification was further studied by means of fluorescence in situ hybridization (FISH) analysis. The immunophenotyping and biochemical analyses showed that the CCSs co-expressed PDGFRalpha and PDGFRbeta, with the latter showing definitively greater protein expression and phosphorylation levels. PDGFRbeta was expressed but not activated in control healthy joint cartilage, in line with no PDGFB detection. Conversely, the KIT gene product did not seem to play a relevant role. These findings, in the absence of activating mutations or an abnormal genomic profile and the presence of PDGFA and PDGFB expression, are consistent with an autocrine/paracrine loop activation of the corresponding receptors. The CCS gene profile described here offers a rationale for the use of RTK inhibitors alone or in combination with chemotherapy, and supports further investigation of RTKs and their downstream signals.
...
PMID:PDGFRalpha, PDGFRbeta and KIT expression/activation in conventional chondrosarcoma. 1647 May 38

Platelet-derived growth factors (PDGFs) and their receptors (PDGFRs) play a vital role in regulating cell growth and angiogenesis. In this study, the expression of the family of PDGFs and PDGFRs in the ovarian corpus luteum were identified and characterized, and an effect of their activity on development of the corpus luteum revealed. Gonadotropin-stimulated immature rats were utilized as a model of induced ovulation, luteogenesis, and pseudopregnancy. Levels of ovarian mRNA for Pdgfb and Pdgfd, and their receptor, Pdgfrb, increased significantly as early as 4 h after human chorionic gonadotropin (hCG) injection in immature rats primed with equine chorionic gonadotropin (eCG). Gonadotropin regulation of Pdgfb expression was confirmed by in vitro promoter-reporter assays, which showed a 2- to 3-fold increase in Pdgfb promoter activity in response to luteinizing hormone (LH). Inhibition studies implicated protein kinase A, phosphatidylinositol 3-kinase and mitogen activated protein kinase signaling pathways in the LH-induced upregulation. In the corpus luteum, PDGFA, PDGFB, PDGFC, and PDGFRA were localized to a population of luteal parenchymal/steroidogenic cells. PDGFRB was expressed primarily in what appeared to be cells of the luteal microvasculature. Intraovarian injection of an inhibitor of PDGF receptor activity, the tyrphostin AG1295, prior to injection of hCG in eCG-primed immature rats resulted in a significant 21.86%+/-11.15% decrease in corpora lutea per treated ovary in comparison to the contralateral vehicle-injected control ovary. In addition, the treated ovary of 3 of 16 rats showed widespread hemorrhage throughout the entire ovary, indicating a possible role for PDGF receptor activity in maintenance of the ovarian vasculature.
...
PMID:Platelet-derived growth factors and receptors in the rat corpus luteum: localization and identification of an effect on luteogenesis. 1710 35

Intraovarian growth factors play a significant role in the regulation of follicular selection and growth. In this study, the presence and localization of all members of the family of platelet-derived growth factors (PDGF) and receptors (PDGFR) were identified and characterized in the rat ovary. In addition, a role was identified for members of this family in contributing towards growth of preantral follicles. Real-time PCR revealed the presence of mRNA for all platelet-derived growth factors (Pdgfa, Pdgfb, Pdgfc and Pdgfd) and receptors (Pdgfra and Pdgfrb) in the rat ovary from birth until 4 wk. In situ hybridization and immunohistochemistry were utilized to identify cell-type expression of PDGFs and PDGFRs in rat ovaries from birth until 4 wk. Shortly after birth, expression of PDGFRA and PDGFC was observed in and around oocyte clusters, and PDGFRB in stromal cells surrounding oocyte clusters. All members were identified in oocytes of primordial and primary follicles, and in cells of the theca layer of primordial to antral follicles. PDGFRA and PDGFA were also localized to some granulosa cells of secondary and antral follicles in ovaries from rats at Days 20 and 24. Thus, localization data suggest both theca-theca and theca-granulosa cell interactions of PDGFs and receptors. Preantral follicles cultured in vitro over 5 days in serum-free medium plus recombinant PDGFAA, PDGFAB, or PDGFBB increased in follicle diameter by 18.32%+/-2.18%, 17.72%+/-2.3%, and 17.6%+/-1.81%, respectively, representing significantly greater increases than for follicles incubated in serum-free medium alone (11%+/-1.57%), and suggesting a role for these growth factors in positively influencing early follicle growth.
...
PMID:Cell-type localization of platelet-derived growth factors and receptors in the postnatal rat ovary and follicle. 1710 37


1 2 3 4 Next >>

---