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:2.7.7.48 (transcriptase)
9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Benign mesenchymal neoplasms associated with rearrangements of the DNA architectural factor gene HMGIC on chromosome 12 include lipomas, uterine leiomyomata, pulmonary chondroid hamartomas, endometrial polyps, salivary gland pleomorphic adenomas, and breast fibroadenomas. Although HMGIC also has been implicated in the pathobiology of aggressive angiomyxoma of the vulva, the molecular mechanisms pertaining to this neoplasm are unclear. Tissue from a recurrent aggressive angiomyxoma was investigated by cytogenetic and expression analysis for HMGIC and HMGIY. The trypsin-Giemsa-banded karyotype showed a clonal translocation between chromosomes 8 and 12 [46,XX,t(8;12)(p12;q15)]. Fluorescence in situ hybridization (FISH) analysis with whole chromosome paint probes for chromosomes 8 and 12 excluded cryptic involvement of other chromosomes. The chromosome 12 breakpoint was mapped with two-color FISH analysis using cosmid probes at the 5' and 3' termini of HMGIC. Both cosmid probes showed hybridization to the normal chromosome 12 and the der(12) chromosome, indicating that the breakpoint was 3' (telomeric) to the gene. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis revealed HMGIC expression in the tumor, and immunohistochemistry localized HMGIC expression to the tumor's spindle cells. Like numerous benign mesenchymal tumors, this locally aggressive tumor is associated with rearrangements near or within HMGIC, but chimeric gene formation was not required for tumorigenesis. Inappropriate expression of this DNA binding protein, however, may be important in the pathobiology of this tumor. Understanding the pathogenetic mechanism may also be helpful in developing new diagnostic tools for identifying residual disease.
...
PMID:Chromosomal translocation t(8;12) induces aberrant HMGIC expression in aggressive angiomyxoma of the vulva. 1155 Feb 85

The bcl-x gene product has two forms, bcl-xl and bcl-xs. The bcl-xl form, similar to bcl-2, inhibits apoptosis. Reverse transcriptase-polymerase chain reaction/single-stranded conformation polymorphism (RT-PCR-SSCP) gel analysis was used to screen for mutations of the bcl-xl transcript of 50 non-Hodgkin's lymphoma (NHL) cases. One missense mutation in a patient with diffuse large B-cell lymphoma was found. Sequence analysis of this case showed that AGC (Ser) was mutated to GGC (Gly) in codon 154. An examination of mutation and/or polymorphism in born marrow samples of this case and 50 normal controls by the RT-PCR-SSCP method could not detect bandshifts. Mutation of the bcl-x gene in NHL has not been reported previously. There is a possibility that mutation of the bcl-x gene play a role in the tumorigenesis of NHL.
...
PMID:Mutation of bcl-x gene in non-Hodgkin's lymphoma. 1183 37

The Atlas human cDNA expression array was used to evaluate gene expression profile changes in the genesis of human lung adenocarcinomas and squamous cell carcinomas. Gene expression changes between adenocarcinomas and squamous cell carcinomas were also analyzed. Of the 588 gene targets, 262 genes were expressed in these tissues and, of these, 45 genes were differentially expressed by at least two-fold in tumor tissues compared to corresponding normal tissues. Semiquantitative reverse-transcriptase polymerase chain reaction was used to confirm gene expression changes. Only those genes that reflected changes in >50% of the analyzed tissues were included in the final analysis. Ultimately, 26 genes were evaluated with 14 genes overexpressed and 12 genes underexpressed compared to matching normal lung tissues. Although similar expression changes were detected in adenocarcinomas and squamous cell carcinomas for most of the genes analyzed, some subtype-specific differences were also found. Genes encoding cell cycle regulators, intracellular signal transducers, cell receptor and adhesion molecules, growth factors, oncogenes, and apoptotic effectors were differentially expressed in this study. These gene expression changes may directly contribute to the initiation or progression of human lung cancer or may be secondary effects of the tumorigenesis process. Regardless, many of these differences may be useful in the diagnosis and/or treatment of this deadly disease.
...
PMID:Differential expression of critical cellular genes in human lung adenocarcinomas and squamous cell carcinomas in comparison to normal lung tissues. 1189 69

GG-62 is a cell line previously thought to be derived from an atypical Ewing tumor (ET). Reverse-transcriptase polymerase chain reaction revealed an in-frame fusion between the Ewing sarcoma gene ( EWS) codon 325 and the activating transcription factor 1 gene ( ATF1) codon 65 which permits the production of chimeric EWS-ATF1 oncoproteins. We also identified the genomic breakpoint resulting from a reciprocal t(12;22)(q13;q12), which is the hallmark of malignant melanoma of soft parts (MMSP). We applied Affymetrix human cancer G110 arrays to compare the gene expression patterns of GG-62 and other cell lines derived from small blue round cell tumors of childhood. Hierarchical clustering of 463 differentially expressed genes distinguished GG-62 from the ETs, as well as the neuroblastomas, and revealed a cluster of 36 upregulated genes. Several of these genes are involved in signal transduction pathways that may be critical for maintaining cell transformation; some examples are avian erythroblastic leukemia viral oncogene homolog 3 ( ERBB3), neuregulin 1 ( NRG1), fibroblast growth factor 9 ( FGF9), and fibroblast growth factor receptor-1 ( FGFR1). Furthermore, genes near the chromosome-12q13 breakpoint exhibited increased expression of GG-62 including ERBB3, NR4A1 (nuclear receptor subfamily 4, group A, member 1), cyclin-dependent kinase 2 ( CDK2), and alpha 5 integrin ( ITGA5). Altogether our findings demonstrate the MMSP derivation of GG-62 and may shed light on the mechanisms of tumorigenesis in this rare disease.
...
PMID:Characterization of the malignant melanoma of soft-parts cell line GG-62 by expression analysis using DNA microarrays. 1202 21

Only a small number of human synovial sarcoma cell lines have been reported, and of those, not all have been fully characterized, especially at the molecular level. We describe here the establishment and characterization of a new human cell line, FU-SY-1, which originated from a monophasic fibrous synovial sarcoma arising in the supinator muscle of a 31-year-old woman. This cell line propagated continuously in vitro for 73 serial passages for more than 36 months. FU-SY-1 cells in vitro were rather small, exhibited a spindle or polygonal shape without conspicuous pleomorphism, and expressed c-Met and hepatocyte growth factor (HGF) as determined by immunocytochemistry. Cytogenetically, FU-SY-1 cells maintained a consistent karyotype: 47, X, +7, t(X;18)(p11.2;q11.2), the same as that of the original tumor specimen. Reverse transcriptase-polymerase chain reaction (RT-PCR) demonstrated a SYT-SSX fusion transcript and expression of c-Met and HGF mRNA in FU-SY-1 cells. A subsequent sequence analysis using the PCR products confirmed that the detected messages were derived from the SYT-SSX1 fusion gene. This cell line, FU-SY-1, established from a monophasic fibrous synovial sarcoma, may therefore be a useful tool for investigation of the mechanisms of tumorigenesis and progression in human synovial sarcomas.
...
PMID:Establishment of a new human synovial sarcoma cell line, FU-SY-1, that expresses c-Met receptor and its ligand hepatocyte growth factor. 1206 44

Conjugated linoleic acid (CLA) has chemoprotective properties in a variety of experimental cancer models. We have previously observed that dietary CLA inhibits colon tumorigenesis induced by 1,2-dimethylhydrazine in rats. In addition, our in vitro studies have shown that CLA inhibits DNA synthesis and induces apoptosis in HT-29 cells, the human colon adenocarcinoma cell line. The insulin-like growth factor (IGF) system regulates the growth of HT-29 cells by an autocrine mechanism. The present study examined whether the growth inhibitory effect of CLA is related to changes in the IGF system in HT-29 cells. To determine whether CLA inhibits IGF-II production, HT-29 cells were incubated in serum-free medium in the presence of various concentrations of CLA. CLA decreased protein levels of both mature and pro IGF-II and IGF-II transcripts. Whereas exogenous IGF-I and IGF-II produced an increase in cell number, neither IGF-I nor IGF-II counteracted the negative growth regulatory effect of CLA. Reverse transcriptase-polymerase chain reaction and Western blot analysis of total cell lysates revealed that CLA decreased IGF-I receptor (IGF-IR) transcript and protein levels in a dose-dependent manner. Immunoprecipitation/Western blot studies revealed that CLA inhibited IGF-I-induced phosphorylation of IGF-IR and insulin-receptor substrate (IRS)-1, recruitment of the p85 regulatory subunit of phosphatidylinositol 3-kinase (PI3K) to IGF-IR, IGF-IR-associated PI3K activity, and phosphorylated Akt and extracellular signal-regulated kinase (ERK)-1/2 levels. In conclusion, the inhibition of cell proliferation and induction of apoptosis by CLA in HT-29 cells may be mediated in part by its ability to decrease IGF-II synthesis and to downregulate IGF-IR signaling and the PI3K/Akt and ERK-1/2 pathways.
...
PMID:Conjugated linoleic acid downregulates insulin-like growth factor-I receptor levels in HT-29 human colon cancer cells. 1288 57

Platelet-derived growth factors (PDGFs) play an integral role in normal tissue growth and maintenance as well as many human pathological states including atherosclerosis, fibrosis, and tumorigenesis. The PDGF family of ligands is comprised of A, B, C, and D chains. Here, we provide the first functional characterization of the PDGF-C promoter. We examined 797 bp of the human PDGF-C promoter and identified several putative recognition elements for Sp1, Ets Egr-1, and Smad. The proximal region of the PDGF-C promoter bears a remarkable resemblance to a comparable region of the PDGF-A promoter (1). Binding and transient transfection analysis in primary vascular smooth muscle cells revealed that PDGF-C, like PDGF-A, is under the transcriptional control of the zinc finger nuclear protein Egr-1 (early growth response-1). Electrophoretic mobility shift analysis using both smooth muscle cell nuclear extracts and recombinant protein revealed that Egr-1 and Sp1 bind this region of the PDGF-C promoter (Oligo C, -35 to -1). Egr-1 competes with Sp1 for overlapping binding sites even when the former is at a stoichiometric disadvantage. Reverse transcriptase PCR and supershift analysis demonstrate that fibroblast growth factor-2 (FGF-2) stimulates both Egr-1 and PDGF-C mRNA expression in a time-dependent and transient manner and that FGF-2-inducible Egr-1 binds the proximal PDGF-C promoter. FGF-2-inducible PDGF-C expression was completely abrogated using catalytic DNA (DNAzymes) targeting Egr-1 but not by its scrambled counterpart. Moreover, using pharmacological inhibitors we demonstrate the critical role of ERK but not JNK in FGF-2-inducible PDGF-C expression. These findings thus demonstrate that PDGF-C transcription, activated by FGF-2, is mediated by Egr-1 and its upstream kinase ERK.
...
PMID:Fibroblast growth factor-2 induction of platelet-derived growth factor-C chain transcription in vascular smooth muscle cells is ERK-dependent but not JNK-dependent and mediated by Egr-1. 1524 55

Progesterone and estradiol play a crucial role in the control of mammary gland proliferation and tumour formation in the dog. However, little is known whether steroid metabolizing enzymes are present within the canine mammary gland that may play a modulating role in the bioavailability of progesterone and estrogen. In this study we investigated the expression of the steroid metabolizing enzymes 5alpha-reductase (type I and type II) and aromatase in relation to hyperplasia or tumorigenesis in the canine mammary tissue. The relative mRNA concentrations were examined by a semi-quantitative reverse-transcriptase PCR analysis (RT-PCR). In addition the affinity of dihydroprogesterone (5alpha-reduced metabolite of progesterone) for canine progesterone receptors was investigated. Quantification of the RT-PCR products revealed that in mammary tumours a significantly higher expression of aromatase is present in comparison to normal mammary tissue. Furthermore, significant decrease in expression of both aromatase and 5alpha-reductase type II enzymes was found in hyperplasic mammary tissue compared to tumours. The changes in expression of type II 5alpha-reductase and aromatase were highly correlated. 5alpha-Reduction of progesterone to dihydroprogesterone resulted in a six-fold less affinity for the canine progesterone receptor. It is concluded that hyperplasia is associated with a decreased expression of type II 5alpha-reductase and aromatase enzymes, whereas in tumours the opposite situation is found.
...
PMID:Mammary steroid metabolizing enzymes in relation to hyperplasia and tumorigenesis in the dog. 1555 10

Osteosarcoma is a malignant bone tumor that commonly affects adolescents and young adults. In the present study a human osteosarcoma cell line, KTHOS, was established from a primary osteosarcoma lesion in the distal femur of a 16-year-old girl. After 106 passages, the KTHOS cell line retained the biological characteristics of osteosarcoma. The KTHOS cells had spindle to pleomorphic cytoplasm with round to ovoid nuclei containing multiple prominent nucleoli, as expected based on the mesodermic origin of osteoblasts. The KTHOS cells were immunoreactive for osteocalcin, osteonectin, stem cell factor (SCF), and KIT (CD117). Reverse transcriptase-polymerase chain reaction indicated that the KTHOS cell line expressed mRNA for SCF and KIT. The KTHOS cells produced relatively high amounts of soluble SCF as determined by enzyme-linked immunosorbent assay. The results suggest that cell proliferation of the KTHOS cell line might be involved in autocrine and/or paracrine loops of the SCF/KIT signaling system. The KTHOS cell line is a novel human osteosarcoma cell line that releases SCF and expresses KIT. This cell line can be used for studies to explore the mechanisms for oncogenesis of human osteosarcomas.
...
PMID:Establishment and characterization of a KIT-positive and stem cell factor-producing cell line, KTHOS, derived from human osteosarcoma. 1569 48

ICAM-5 (telencephalin) is an intercellular adhesion molecule reported to be expressed only in the somatodendritic membrane of telencephalic neurons. We recently identified high ICAM-5 expression in a cDNA array study of head and neck neoplasms with a propensity for perineural invasion. To determine the association of this gene in tumorigenesis and perineural invasion, we analyzed the expression and functional status of ICAM-5 mRNA transcripts in 30 different human cancer cell lines and 25 head and neck squamous carcinoma specimens by reverse-transcriptase polymerase chain reaction (cell lines and specimens) and in vitro functional assays (cell lines). ICAM-5 transcripts were detected in 28 (93%) of 30 cell lines derived from primary head and neck, colon, thyroid, cervical, pancreatic, skin, and adenoid cystic carcinomas. In cell lines, small interfering RNA blocked ICAM-5 expression and inhibited cell proliferation. Treatment with the phosphatidylinositol 3'-kinase (PBK) inhibitor LY294002 resulted in ICAM-5 down-regulation. In tissue specimens, none of the 25 histologically normal oral mucosal specimens had detectable ICAM-5 level, whereas 16 (64%) of the 25 matched primary squamous carcinomas showed expression. Carcinoma specimens high ICAM-5 expression had a high incidence of perineural invasion. Our study indicates that ICAM-5 may play a role in tumorigenesis and perineural invasion, most likely through the P13K/Akt-signaling pathway.
...
PMID:ICAM-5 (telencephalin) gene expression in head and neck squamous carcinoma tumorigenesis and perineural invasion! 1597 20


<< Previous 1 2 3 4 5 Next >>

---