Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017636 (glioblastoma)
 18,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To define the neural-specific expression of rat repetitive identifier (ID) DNA, we co-transfected an intron B subclone of the rat growth hormone (rGH) gene, containing a tandem array of two type 2 repeats and a single ID monomer, and a plasmid conferring neomycin resistance into human SK-N-MC neuroblastoma, HeLa epidermal carcinoma, 293 kidney and 251 MG glioblastoma cells. Transcript analysis from both individual and pools of G418-resistant cells revealed that rGH intron B repeats were expressed only in SK-N-MC neuroblastoma cells as small, cytoplasmic RNAs of 85, 110, 155 and 180 bases. Primer-extension studies show these repetitive RNAs to contain a common 5' end that maps precisely to the beginning of the ID element and that type 2 transcripts are not stably expressed. However, ID DNA expression from two other transfected plasmids, each containing only the ID core sequence, was not restricted to the SK-N-MC cell line. These data show that the transfected rGH ID sequence is selectively expressed in a neural-specific manner resulting in BC-like RNAs, and furthermore, suggest that flanking DNA may play a role in cell-specific expression of certain repetitive DNA elements.
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PMID:Cell-specific expression of transfected brain identifier repetitive DNAs. 245 42

To establish stable culture conditions which support persistence of the human cytomegalovirus (HCMV) genome in a latent state, the expression of the bacterial neomycin phosphotransferase (neo) from HCMV recombinants was used for selection. Different cell lines were infected with HCMV recombinants. The human glioblastoma line U138-MG was rendered resistant to G418 and retained the viral genome. More than 90% of the cells expressed the viral IE1 protein of 72 kDa for a culture period of 18 months. Many fewer cells expressed IE2-encoded proteins. No late gene expression or infectious virus was detectable. IE2 gene expression in latently infected cells appeared to be restricted at the level of RNA accumulation. Treatment with TPA or retinoic acid led to enhanced expression of the IE2 gene and the early genes encoding pp65 (UL83) and p52 (UL44). Superinfection with wild-type HCMV led to replication of neo-recombinant virus, indicating that replication-competent virus had been retained in latently infected U138-MG and that the cells had kept their permissive phenotype. Latent HCMV infection in U138-MG cells provides a useful model system for studying the role of particular viral and cellular genes in latent and permissive infections.
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PMID:Reduced levels of IE2 gene expression and shutdown of early and late viral genes during latent infection of the glioblastoma cell line U138-MG with selectable recombinants of human cytomegalovirus. 809 45

Transforming growth factor-beta (TGF-beta) has been implicated as a potent growth regulator; the degree of responses to it, whether positive or negative, generally correlates with the stage of cell differentiation in various cell types. We examined the effect of the p53 gene, which participates in the control of cell-cycle progression, on the expression of human TGF-beta. The human glioblastoma cell line SNB-19, which expresses the latent form of TGF-beta, was transfected with a retroviral vector containing wild-type p53 (wt-p53) or p53 with a mutation (mut-p53) at codon 273. Stable G418-resistant SNB-19 clones were isolated. The growth kinetics of wt-p53 transfectants were suppressed compared with those of parental cells, vector transfectants, or mut-p53 transfectants, as assayed by growth-curve measurements and 3H-thymidine incorporation; however, RNA dot blot and Western blot analyses demonstrated that wt-p53 and mut-p53 transfectants expressed higher amounts of TGF-beta 1 and TGF-beta 2 mRNA and intracellular TGF-beta isoform proteins, respectively, than parental cells. By means of the biological assay for active TGF-beta (Mv1Lu cell-growth-inhibition assay), we observed that both transfectants produced active TGF-beta, whereas the parental cells produced only the latent form. These results suggest that, while only the wt-p53 gene inhibits tumor-cell progression, both wt-p53 and codon 273-mutated p53 can cause increased TGF-beta expression.
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PMID:Retroviral-mediated transduction of p53 gene increases TGF-beta expression in a human glioblastoma cell line. 811 73

The construction of a new retroviral vector, pSKV, is described. This vector carries two unique cloning sites, located between two Moloney leukemia virus-derived LTR, into which genes of interest may be introduced. The gene encoding hygromycin resistance (HyR) was subsequently introduced into one of the two sites, producing a second vector (pSKV/HyR) containing a unique SfiI site for the introduction of cDNA clones under the control of the cytomegalovirus (CMV) promoter (P-CMV). The cDNA (mH13), encoding a protein that has been shown to serve as a murine ecotropic retroviral receptor in transient assays, was cloned into the SfiI site (pSKV/HyR/mH13). Both constructs can be packaged into retroviral particles following transfection into an appropriate packaging cell line. Stable transfectants of the human glioblastoma cell line (U118MG) carrying each of these two constructs were generated by transfection and subsequent Hy selection. Clones expressing both the selectable marker and the mH13 gene, but not those expressing only the selectable marker, are shown to be susceptible to infection with murine ecotropic retroviral particles. These cells (HyR and mH13 positive) were then exposed to CRE/Xtk culture supernatant, a packaging cell line producing ecotropic retroviral particles carrying the HSV-TK (Herpes simplex virus-thymidine kinase) and neoR (neomycin-resistance) genes. Selection was in the presence of G418. In vitro growth of the U118MG/HyR/mH13/TK cells, but not that of the U118MG/HyR/mH13 cells, was inhibited by ganciclovir (GCV), indicating the successful transfer of HSV-TK by infection of human cells with murine retroviruses via the mH13 product.
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PMID:Infection of human cells by murine ecotropic viruses: retroviral vectors carrying the hygromycin resistance-encoding gene. 866 55

Calmodulin (CaM) is involved in cellular processes that are vital to cell proliferation and viability. Elevated CaM content is seen in transformed cells. Anti-CaM compounds alone are cytotoxic to tumor cells and are synergistic with certain cancer chemotherapeutic agents. However, all known CaM antagonists are nonselective, complicating interpretation of these studies. To more rigorously analyze the relationship between CaM protein expression and the behavior of cancer cells, tumor-derived cell lines were engineered such that CaM concentration could be manipulated by overexpressing CaM RNA. A full-length rat CaM I cDNA was inserted into the mammalian expression vector pMTCB6+ so that either CaM mRNA (sense) or antisense RNA was expressed under the control of an inducible metallothionein promoter. Constructs were introduced into C6 glioblastoma cells by liposome-mediated transfection and colonies were selected in G418. Significantly fewer clones were recovered from transfections with antisense vectors compared to CaM sense RNA or control (empty) vector alone. This difference was attributed to the cytotoxic effects of antisense CaM RNA as opposed to differences in transfection efficiencies. CaM expression was analyzed at the RNA level by Northern blotting and CaM protein concentrations were quantitated by immunofluorescence. Clones were identified in which CaM protein could be increased or decreased following exposure to zinc ions. Changes in CaM mRNA preceded changes in CaM protein by several hours. Overexpression of CaM had no significant effects on the growth of C6 cells. However, reductions in CaM lead to decreased growth rates of C6 cells and lowered cell viability.
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PMID:The effects of altered cellular calmodulin expression on the growth and viability of C6 glioblastoma cells. 911 56

It is extremely rare for brain glioblastoma to metastasize extracranially. To elucidate whether glioblastoma cells remain non-metastatic when ectopically transplanted and CD44v gene is introduced, glioblastoma RG2-m cells were transfected with CD44v gene sequence encompassing v3-v10. After selection in culture medium with G418, CD44v expressing RG2-a cells were cloned. With RG2-a and its parental counterpart RG2-m, a series of experimental metastasis assays were performed in syngeneic F344 rats. When inoculated subcutaneously and in the foot-pad, both RG2-m and RG2-a cells metastasized spontaneously to the regional lymph nodes and lungs. However, metastasis of RG2-a was more severe and more organs were involved when compared to that of the parental RG2-m cells. The results indicate that glioblastoma becomes metastatic if extracranially transplanted and expression of CD44v would further enhance its metastatic patential.
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PMID:[Enhanced metastatic potential of rat RG2 glioblastoma cells transfected with CD44v (meta-1) sequence]. 938 71

Increased expression of matrix metalloproteinases (MMPs) has been associated with human glioblastoma tumor progression. In this study, we sought to down-regulate MMP-9 expression by stably transfecting a high-grade glioblastoma cell line with a plasmid vector capable of expressing an antisense transcript complementary to a 528-bp segment at the 5' end of human MMP-9 cDNA. Stable transfectants were obtained through selection with G418. Of the clones transfected with vector, sense, and antisense constructs, Northern blotting, Western blotting, and gelatin zymography showed that MMP-9 expression was significantly reduced only in the antisense-transfected cells. A Matrigel invasion assay revealed marked reductions in invasiveness for the antisense clones relative to the parental, vector, and sense clones. Cocultures of tumor spheroids and fetal rat brain aggregates showed that the antisense-transfected stable clones showed no invasion of the rat brain aggregates; in contrast, 90% of the parental, vector, and sense clones invaded the rat brain aggregates. Intracerebral injection of antisense stable transfectants in nude mice produced no tumors or very small tumors, but intracerebral injection of parental or vector clones did produce tumors. These results suggest that MMP-9 expression is essential for the invasiveness of glioblastoma cells.
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PMID:Selective suppression of matrix metalloproteinase-9 in human glioblastoma cells by antisense gene transfer impairs glioblastoma cell invasion. 1115 78

The introduction of chromosome 10p into human glioblastoma or prostate cancer cells has been demonstrated to suppress their malignant phenotype, suggesting the presence of glioma or prostate tumor suppressor genes on 10p. As a resource for the fine mapping of these genes, a series of human-rodent hybrid cell lines containing single transferable fragments (STFs) of 10p were constructed. Normal chromosome 10 tagged with a neomycin-resistance gene on its short arm was fragmented by gamma-irradiation of 5-10krad, transferred into mouse L cells or Chinese hamster ovary cells by microcell-mediated chromosome transfer (MMCT), and then selected against G418. Thirty-three independent rodent-human hybrids carrying various-sized STFs were obtained. Polymerase chain reaction (PCR)-based genotyping revealed that these STFs contained the whole, or portions, of a 43-cM region on 10p14-pter and could be defined by 19 sequence-tagged-site (STS) markers. Using this panel of hybrids as donors for further MMCT, genes on the refined fragments could be transferred into other cells. This hybrid panel would therefore be a useful resource for the fine mapping of the genes on 10p14-pter to segments of about 2.4 cM by functional complementation.
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PMID:Construction of human-rodent hybrid cells containing single transferable fragments of human chromosome 10p. 1118 48