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SRP033518
Mus musculus
8 Downloadable Samples
Illumina HiSeq 2000
Description
Recently, attenuated Semliki Forest virus vector VA7 completely eliminated type I interferon (IFN) unresponsive human U87 glioma xenografts while IFN responsive mouse GL261 and CT-2A gliomas proved refractory to the oncolytic virotherapy. Here we describe in two clones of a well established Balb/c mouse tumor cell line, CT26 murine colon carcinoma, diametrically opposed IFN responsiveness and sensitivity to oncolytic virus. Both CT26WT and CT26LacZ clones secreted biologically active type I IFN in vitro upon infection but virus replication was self-limiting only in CT26WT cells. Total transcriptome sequencing (RNA-Seq) and western blotting experiments revealed that in sharp contrast to CT26LacZ cells, CT26WT cells had strong constitutive expression of 56 different genes associated with pattern recognition and type I interferon signaling pathways, spanning two reported anti-RNA virus gene signatures and22 genes that have been reported to have direct anti-Alphaviral activity. Correspondingly, only CT26LacZ tumors were infectable in vivo, resulting in rapid central necrosis of the tumors by 96 hours post infection and complete tumor eradication both in immunocompetent and in SCID mice. CT26LacZ tumor eradication by oncolysis induced 100% protective immunity against homologous CT26LacZ challenge but only 50% protection against heterologous CT26WT challenge, indicating LacZ immune dominance over shared antigens. We believe the two clone CT26 system described herein constitutes a challenging yet realistic model for clonally and immunologically heterogeneous cancer where a strong therapy efficacy bias toward sensitive tumor subpopulations might falsely predict therapeutic success on a broad patient scale highlighting the necessity of successful pre-screening for responsive tumors. Overall design: RNA-Seq in CT26 tumor cell line
Publication Title
Clonal variation in interferon response determines the outcome of oncolytic virotherapy in mouse CT26 colon carcinoma model.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 32 Downloadable Samples
Affymetrix Human Gene 1.1 ST Array (hugene11st), Illumina Genome Analyzer IIx
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Genome-wide screen of cell-cycle regulators in normal and tumor cells identifies a differential response to nucleosome depletion.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 32 Downloadable Samples
- Illumina Genome Analyzer IIx, Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
Gene-expression in siRNA treated U2OS and hTERT-RPE1 cells showed that CASP8AP2, NPAT and HINFP do not regulate expression of each other, and do not have any common target genes, except histones. Most histone genes are downregulated in U2OS cells following loss of CASP8AP2, NPAT or HINFP. In normal cells, highly-expressed histone genes were downregulated, albeit less than in tumor cells following loss of CASP8AP2. The p53 target genes were upregulated relatively late, clearly after the changes in expression of histone genes were observed.
Publication Title
Genome-wide screen of cell-cycle regulators in normal and tumor cells identifies a differential response to nucleosome depletion.
Sample Metadata Fields
Cell line
View Samples