Vitamin D3 up-regulating protein 1 (VDUP1) antisense DNA, regulates tumorigenicity and melanogenesis of murine melanoma cells via regulating the expression of fas ligand and reactive oxygen species

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. (C) 2003 Elsevier Science B.V. All rights reserved.