VDUP1 upregulated by TGF-beta1 and 1,25-dihydorxyvitamin D3 inhibits tumor cell growth by blocking cell-cycle progression

Oncogene. 2003 Jun 26;22(26):4035-46. doi: 10.1038/sj.onc.1206610.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Animals
  • Blotting, Northern
  • Calcitriol / metabolism*
  • Carrier Proteins / biosynthesis*
  • Cell Cycle
  • Cell Differentiation
  • Cell Division
  • Cell Line
  • Cyclin A / metabolism
  • Cyclin A2
  • DNA-Binding Proteins / metabolism
  • Disease Progression
  • Fanconi Anemia / metabolism
  • Flow Cytometry
  • G1 Phase
  • Genes, Reporter
  • HL-60 Cells
  • Histone Deacetylase 1
  • Histone Deacetylases / metabolism
  • Humans
  • In Situ Hybridization
  • Interleukin-3 / metabolism
  • Jurkat Cells
  • Kruppel-Like Transcription Factors
  • Mice
  • Microscopy, Fluorescence
  • Neoplasms / metabolism*
  • Promoter Regions, Genetic
  • Promyelocytic Leukemia Zinc Finger Protein
  • Repressor Proteins*
  • Resting Phase, Cell Cycle
  • Retroviridae / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Thioredoxins*
  • Time Factors
  • Transcription Factors / metabolism
  • Transcription, Genetic
  • Transfection
  • Transforming Growth Factor beta / metabolism*
  • Transforming Growth Factor beta1
  • Tumor Cells, Cultured
  • Up-Regulation*
  • Zinc Fingers

Substances

  • CCNA2 protein, human
  • Carrier Proteins
  • Cyclin A
  • Cyclin A2
  • DNA-Binding Proteins
  • Interleukin-3
  • Kruppel-Like Transcription Factors
  • Promyelocytic Leukemia Zinc Finger Protein
  • Repressor Proteins
  • Rog protein, mouse
  • TGFB1 protein, human
  • TXNIP protein, human
  • TZFP protein, human
  • Tgfb1 protein, mouse
  • Transcription Factors
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta1
  • Zbtb16 protein, mouse
  • ZBTB16 protein, human
  • Thioredoxins
  • HDAC1 protein, human
  • Histone Deacetylase 1
  • Histone Deacetylases
  • Calcitriol