Characterization of the canine mda-7 gene, transcripts and expression patterns
Autor: | David T. Curiel, Devanand Sarkar, Paul B. Fisher, R. Curtis Bird, Swadesh K. Das, Bruce F. Smith, Maninder Sandey |
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Rok vydání: | 2014 |
Předmět: |
Keratinocytes
Gene isoform Signal peptide Molecular Sequence Data Biology Article Conserved sequence Dogs Genetics Animals RNA Messenger skin and connective tissue diseases Gene Cells Cultured Conserved Sequence Regulation of gene expression Messenger RNA Base Sequence Reverse Transcriptase Polymerase Chain Reaction Interleukins Alternative splicing DNA General Medicine Molecular biology Alternative Splicing Cell killing Gene Expression Regulation |
Zdroj: | Gene. 547:23-33 |
ISSN: | 0378-1119 |
Popis: | Human melanoma differentiation associated gene-7/interleukin-24 (mda-7/IL-24) displays potent growth suppressing and cell killing activity against a wide variety of human and rodent cancer cells. In this study, we identified a canine ortholog of the human mda-7/IL-24 gene located within a cluster of IL-10 family members on chromosome 7. The full-length mRNA sequence of canine mda-7 was determined, which encodes a 186-amino acid protein that has 66% similarity to human MDA-7/IL-24. Canine MDA-7 is constitutively expressed in cultured normal canine epidermal keratinocytes (NCEKs), and its expression levels are increased after lipopolysaccharide stimulation. In cultured NCEKs, the canine mda-7 pre-mRNA is differentially spliced, via exon skipping and alternate 5′-splice donor sites, to yield five splice variants (canine mda-7sv1, canine mda-7sv2, canine mda-7sv3, canine mda-7sv4 and canine mda-7sv5) that encode four protein isoforms of the canine MDA-7 protein. These protein isoforms have a conserved N-terminus (signal peptide sequence) and are dissimilar in amino acid sequences at their C-terminus. Canine MDA-7 is not expressed in primary canine tumor samples, and most tumor derived cancer cell lines tested, like its human counterpart. Unlike human MDA-7/IL-24, canine mda-7 mRNA is not expressed in unstimulated or lipopolysaccharide (LPS), concanavalin A (ConA) or phytohemagglutinin (PHA) stimulated canine peripheral blood mononuclear cells (PBMCs). Furthermore, in-silico analysis revealed that canonical canine MDA-7 has a potential 28 amino acid signal peptide sequence that can target it for active secretion. This data suggests that canine mda-7 is indeed an ortholog of human mda-7/IL-24, its protein product has high amino acid similarity to human MDA-7/IL-24 protein and it may possess similar biological properties to human MDA-7/IL-24, but its expression pattern is more restricted than its human ortholog. |
Databáze: | OpenAIRE |
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