VDUP1 upregulated by TGF-beta 1 and 1,25-dihydorxyvitamin D-3 inhibits tumor cell growth by blocking cell-cycle progression

Abstract

Vitamin D-3 upregulated protein 1 (VDUP1) is a 1,25-dihydroxyvitamin D-3 (1,25(OH)(2)D-3) upregulated protein, and it is induced by various stresses. In human tumor tissues, VDUP1 expression was downregulated. Upon stimulation by growth-inhibitory signals such as TGF-beta1 and 1,25(OH)(2)D-3, its expression was rapidly upregulated as the cell growth was retarded. The transfection of VDUP1 in tumor cells reduced cell growth. The VDUP1 expression was also increased when the cell-cycle progression was arrested. Transfection of VDUP1 induced cell-cycle arrest at the G0/G1 phase, indicating that VDUP1 possesses a tumor-suppressive activity. In addition, it was found that VDUP1 interacted with promyelocytic leukemia zinc-finger, Fanconi anemia zinc-finger, and histone deacetylase 1, which are known to be transcriptional corepressors. VDUP1 itself suppressed IL-3 receptor and cyclin A2 promoter activity. Taken together, these results suggest that VDUP1 is a novel antitumor gene which forms a transcriptional repressor complex.