| Gene set: IFNA_HCC_TOLERANT_DOWN (C2:PERT:0135) | | Standard name | IFNA_HCC_TOLERANT_DOWN |
| Systematic name | C2:PERT:0135 |
| Brief description | Genes highly expressed in interferon-sensitive hepatoma cell lines (HKCI-1-4,HepG2,Hep3B,PCL/PRF/5) vs. resistant cell lines (HKCI-C1-3) |
| Category | C2: Curated |
| Sub-category | PERT: Experimental pertuberation |
| Full description or Abstract | Toggle abstract view PURPOSE: Treatment with IFN-alpha therapy has been shown to exhibit
antitumor effects on patients with hepatocellular carcinoma (HCC).
However, individual responses remained unpredictable because of
the frequent presence of intrinsic or acquired IFN-alpha resistance.
Hence, delineation of molecular targets implicated in the resistant
pathway holds value in refining the therapeutic benefits of IFN-alpha.
EXPERIMENTAL DESIGN: The current study analyzed the effect of
IFN-alpha in human HCC cells. Three hepatitis C virus (HCV)-related,
five hepatitis B virus (HBV)-related and two non-B non-C-related
cell lines were subjected to IFN-alpha treatment and the cytotoxic
effect on cell viability was measured. Further analysis by cDNA
microarray and quantitative reverse transcription-PCR were conducted
to examine the gene expression changes that mediated the IFN-alpha
resistance observed. RESULTS: According to the IC(50) values determined,
HCV-related cell lines indicated distinct resistance (IC(50),
389-1468 units/mL) compared with the HBV-related (IC(50), 11-77
units/mL) and non-B non-C-related cell lines (IC(50), 24-108 units/mL).
Unsupervised hierarchical clustering on array data indicated three
HCV-related cell lines to cluster independently from the sensitive
cell lines, suggesting discrete features in association with IFN-alpha
tolerance. Moreover, Significance Analysis of Microarrays analysis
indicated the differential expression of 149 expressed sequence
tags that represented 51 up-regulated and 98 down-regulated genes
in the resistant cell lines. Comparing the temporal pattern of
gene expression between 6- and 24-hour treatments, candidate genes
that were considerably induced with time were further highlighted
in the tolerant HCV-related cell lines. These candidates were
verified by quantitative reverse transcription-PCR, which confirmed
the down-regulation of UBA2, ZNF185, and FOXF1 and up-regulation
of UBE4B in the drug-tolerant cells. CONCLUSIONS: Our present
study showed that the insensitivity to IFN-alpha therapy in HCC
cells is associated with drug-inducible transcriptional alterations.
Furthermore, our investigation highlighted potential candidate
genes in conferring an anti-apoptotic effect toward IFN-alpha
treatment. |
| Publication URL | 15709204 |
| External links | na |
| Keywords & MeSH headings | Oligonucleotide Array Sequence Analysis/methods,Gene Expression Profiling,Cell Survival/drug effects,pharmacology,Transcription,Drug,Humans,Tumor Necrosis Factor-alpha,Dose-Response Relationship,Hepatitis C/pathology/virology,Genetic/genetics,genetics,Gene Expression Regulation,Neoplastic/drug effects,Neoplasm,Liver Neoplasms/genetics/pathology/virology,Cell Division/drug effects,Drug Resistance,Cluster Analysis |
| Organism | Human |
| Contributed by | Yujin Hoshida |
| Source platform | Gene_Symbol |
| Download | grp|xml|map |
| Genes | 37 genes, 37 accessions (Toggle view) | Gene | Title | Links |
|---|
| PLAUR | plasminogen activator, urokinase receptor | Source|GeneCards | | PDK2 | pyruvate dehydrogenase kinase, isoenzyme 2 | Source|GeneCards | | PWP1 | nuclear phosphoprotein similar to S. cerevisiae PWP1 | Source|GeneCards | | DUSP3 | dual specificity phosphatase 3 (vaccinia virus phosphatase VH1-related) | Source|GeneCards | | PSMD8 | proteasome (prosome, macropain) 26S subunit, non-ATPase, 8 | Source|GeneCards | | NOL5A | nucleolar protein 5A (56kDa with KKE/D repeat) | Source|GeneCards | | ATP6V0B | ATPase, H+ transporting, lysosomal 21kDa, V0 subunit c'' | Source|GeneCards | | HNRPF | heterogeneous nuclear ribonucleoprotein F | Source|GeneCards | | LZTR1 | leucine-zipper-like transcriptional regulator, 1 | Source|GeneCards | | RNF19 | ring finger protein 19 | Source|GeneCards | | MRPS35 | mitochondrial ribosomal protein S35 | Source|GeneCards | | IDUA | iduronidase, alpha-L- | Source|GeneCards | | MKLN1 | muskelin 1, intracellular mediator containing kelch motifs | Source|GeneCards | | SBF1 | SET binding factor 1 | Source|GeneCards | | UBA2 | SUMO-1 activating enzyme subunit 2 | Source|GeneCards | | DEFA1 | defensin, alpha 1 | Source|GeneCards | | ITGA11 | integrin, alpha 11 | Source|GeneCards | | PSCD4 | pleckstrin homology, Sec7 and coiled-coil domains 4 | Source|GeneCards | | NOG | noggin | Source|GeneCards | | FOXF1 | forkhead box F1 | Source|GeneCards | |
| PIGS | phosphatidylinositol glycan, class S | Source|GeneCards | |
| PRKACB | protein kinase, cAMP-dependent, catalytic, beta | Source|GeneCards | | HMGN1 | high-mobility group nucleosome binding domain 1 | Source|GeneCards | | GRIN2A | glutamate receptor, ionotropic, N-methyl D-aspartate 2A | Source|GeneCards | | ZNF32 | Zinc finger protein 32 (KOX 30) | Source|GeneCards | | HMGB1 | high-mobility group box 1 | Source|GeneCards | | PAK7 | p21(CDKN1A)-activated kinase 7 | Source|GeneCards | | TTR | transthyretin (prealbumin, amyloidosis type I) | Source|GeneCards | | POR | P450 (cytochrome) oxidoreductase | Source|GeneCards | | EMR1 | egf-like module containing, mucin-like, hormone receptor-like 1 | Source|GeneCards | | MGMT | O-6-methylguanine-DNA methyltransferase | Source|GeneCards | | MSH2 | mutS homolog 2, colon cancer, nonpolyposis type 1 (E. coli) | Source|GeneCards | | ZNF185 | zinc finger protein 185 (LIM domain) | Source|GeneCards | |
| LRP6 | low density lipoprotein receptor-related protein 6 | Source|GeneCards |
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