Abstract
The expression of vitamin D(3) up-regulating protein-1 (VDUP1) was up-regulated by 1alpha,25-dihydroxyvitamin D(3) (VD3) treatment in B16 mouse melanoma cells. The functional effect of VDUP1 on B16F10 melanoma cells was demonstrated by reduction of Fas ligand and CD44 expression in cells transfected with VDUP1 antisense cDNA. Furthermore, intracellular reactive oxygen species level and cell proliferation were decreased in antisense transfectants compared with those in vector controls. However, melanin synthesis was up-regulated in antisense transfectants. In addition, VDUP1 antisense transfectants showed an increased susceptibility to natural killer (NK) cells in vitro. When VDUP1 antisense transfectants were implanted into syngeneic mice, significant reduction of tumor cell growth was observed with the infiltrate of T cells and NK cells in tumor area. Taken together, these results demonstrate that VDUP1 has critical physiological roles and can be a novel therapeutic target for melanoma.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Carrier Proteins / drug effects
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Carrier Proteins / genetics
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Carrier Proteins / immunology
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Carrier Proteins / metabolism*
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Cell Line, Tumor
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DNA, Antisense
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Fas Ligand Protein
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Flow Cytometry
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Gene Expression Regulation, Neoplastic
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Hyaluronan Receptors / biosynthesis
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Immunoblotting
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Immunohistochemistry
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Killer Cells, Natural / immunology
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Male
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Melanins / biosynthesis
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Melanoma / immunology
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Melanoma / metabolism*
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Membrane Glycoproteins / metabolism*
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Mice
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Polyamines
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Reactive Oxygen Species / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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Thioredoxins*
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Transfection
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Vitamin D / analogs & derivatives*
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Vitamin D / pharmacology
Substances
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2,10-dioximino-3,9-dimethyl-4,8-diazaundeca-3,8-diene
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Carrier Proteins
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DNA, Antisense
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FASLG protein, human
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Fas Ligand Protein
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Fasl protein, mouse
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Hyaluronan Receptors
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Melanins
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Membrane Glycoproteins
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Polyamines
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Reactive Oxygen Species
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TXNIP protein, human
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dihydroxy-vitamin D3
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Vitamin D
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Thioredoxins