Expression of the caspase-8 gene in neuroblastoma cells is regulated through an essential interferon-sensitive response element (ISRE).
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Caspase 8↗
Biomedical subjects
A De Ambrosis
Publications and source records attributed to A De Ambrosis.
Lack of HLA-class I antigens in human neuroblastoma cells: analysis of its relationship to TAP and tapasin expression.
We studied the constitutive and the interferon (IFN)-gamma-induced expression of HLA class I antigen heavy chain, beta2-microglobulin (beta2m), TAP-1, TAP-2 and tapasin in a panel of eleven neuroblastoma cell lines. Surface expression of HLA class I antigens was low in eight out of eight neuroblastoma cell lines bearing MYC-N amplification and/or 1p deletion, while two out of three neuroblastoma cell lines lacking these genetic alterations showed normal expression. IFN-gamma treatment restored HLA class I antigen surface expression in all neuroblastoma cell lines. Eight out of 11 neuroblastoma cell lines did not express TAP-1 mRNA and three of them also lacked TAP-2 mRNA. beta2 m mRNA was barely detectable or absent in five neuroblastoma cell lines, while tapasin mRNA was always expressed. IFN-gamma upregulated the expression of HLA class I heavy chain, beta2 m, TAP-1, TAP-2 and tapasin, as detected at mRNA or protein level. Post-transcriptional events were involved in altered TAP-1 and beta2 m expression in one peculiar neuroblastoma cell line. These data indicate that multiple mechanisms play a role in the HLA class I antigen-deficient phenotype of human neuroblastoma.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
The combined action of IL-15 and IL-12 gene transfer can induce tumor cell rejection without T and NK cell involvement.
The cooperative antitumor effects of IL-12 and IL-15 gene transfer were studied in the N592 MHC class I-negative small cell lung cancer cell line xenotransplanted in nude mice. N592 cells engineered to secrete IL-15 displayed a significantly reduced tumor growth kinetics, and a slightly reduced tumor take rate, while N592 engineered with IL-12 displayed only minor changes in their growth in nude mice. However, N592 cells producing both cytokines were completely rejected, and produced a potent local bystander effect, inducing rejection of coinjected wild-type tumor cells. N592/IL-12/IL-15 cells were completely and promptly rejected also in NK-depleted nude mice, while in granulocyte-depleted animals a slight delay in the rejection process was observed. Immunohistochemical analyses of the N592/IL-12/IL-15 tumor area in intact nude mice revealed the presence of infiltrating macrophages, granulocytes, and NK cells, and expression of inducible NO synthase and of secondary cytokines such as IL-1beta, TNF-alpha, and IFN-gamma, and at higher levels GM-CSF, macrophage-inflammatory protein-2, and monocyte chemoattractant protein-1. In NK cell-depleted nude mice, numerous macrophages and granulocytes infiltrated the tumor, and a strong expression of macrophage-inflammatory protein-2 and inducible NO synthase was also observed. Finally, macrophages cocultured with N592/IL-12/IL-15 produced NO in vitro, and inhibited tumor cell growth, further suggesting their role as effector cells in this model.
Adjuvants, Immunologic↗
Analysis of a viral integration event in a CG-rich region at the 1p36 human chromosomal site.
The preinsertion site of an adenovirus-5/simian virus 40 recombinant construct (Ad5/SV40) has been cloned and sequenced. Our data suggest that viral integration has occurred in a genomic region which has been the target of multiple events of Alu element retropositions within a TAA minisatellite. Extensive homologies between the left viral end and the host cellular DNA were also observed. The compositional similarity between Adenoviridae and the region of viral integration is consistent with the observed insertion of exogenous DNA in isochores of similar composition [G. Bernardi, Annu. Rev. Genet. 23 (1989) 637-661].
Base Sequence↗
Chromatin structure, DNA methylation, and gene expression at sites of viral integration in human fibroblasts. Implications for chromosomal fragility.
We analyzed the structural and functional properties of a chromosomal region in which a recombinant hybrid virus adenovirus 5/SV40 preferentially integrates. Our results demonstrated that the structure of the cellular targets for DNA and RNA viruses is very similar and that the cellular sequence flanking the integrated virus possesses, simultaneously, all the features postulated to be the molecular basis for chromosomal fragility.
Adenoviridae↗
Preferential integration of the Ad5/SV40 hybrid virus at the highly recombinogenic human chromosomal site 1p36.
Human fibroblasts transformed with an adenovirus-5/simian virus 40 recombinant construct (Ad5/SV40) were analyzed to determine the chromosomal site(s) of virus integration. This was firstly done by in situ hybridization using metaphase and prometaphase chromosomes and 125I-labeled Ad5 DNA. Out of seven transformed cell lines (six of clonal origin and one uncloned), six were proven to have integrated the viral genome at the short- or the long-subtelomeric regions of autosome 1, two regions known to include chromosomal modification sites induced by acute infection with Ad12. Characterization of the integration sites was carried out by restriction analysis. Transformed cell lines with the same major chromosomal integration site were found to have the viral genome inserted in restriction fragments of different size, indicating that viral integration has occurred at different sites within a relatively small chromosomal region. Molecular studies carried out on one of the transformed cell lines (H13.1) gave an independent confirmation of the viral integration at the subterminal region of autosome 1 short arm. Nucleotide sequencing at this cellular-viral junction has shown that the virus has integrated within tandemly repeated Alu-like elements and that the cellular flanking sequences have several homologies with variable number of tandem repeats core sequences. Many possible open reading frames were identified in the DNA segment adjacent to the Alu-like elements.
Adenoviruses, Human↗
Chromosome aberrations associated with CAD gene amplification in Chinese hamster cultured cells.
Eleven sublines with increasing resistance to N-phosphonacetyl-L-aspartate (PALA) were isolated from the V79,B7 Chinese hamster cell line. Aspartate transcarbamylase activity and CAD gene copy number increased with increasing resistance of sublines. In situ hybridization with a DNA probe for the CAD gene showed that the amplified sequences resided in the terminal region of a marker chromosome with elongated q arms. This region stained homogeneously after G-banding. A high incidence of both numerical and structural chromosome aberrations was found in PALA-resistant cells. In hyperdiploid and polyploid cells, containing 2 copies of the marker chromosome, dicentrics were found at a very high frequency. As indicated by in situ hybridization and G-banding, they originated from a rearrangement involving 2 homologous marker chromosomes.
Animals↗
Nucleosomal repeat length in active and inactive genes.
Nucleosomal repeat lengths of total chromatin, H4 histone and beta-DR genes have been measured in logarithmically growing HeLa cells. We have detected significant differences in nucleosomal spacing between inactive chromatin and chromatin regions actively engaged in transcription. These differences are also maintained in metaphase chromosomes at times when transcription ceases although a shortening in nucleosomal repeat length is observed in active and inactive chromatin. These observations support a model where DNA-core histone interactions are temporarily altered to allow selective remodelling of chromatin organization.
Chromatin↗