Sp1 is involved in 8-chloro-adenosine-upregulated death receptor 5 expression in human hepatoma cells

  • Authors:
    • Minmin Sun
    • Jinchun Zhang
    • Shilian Liu
    • Yanxin Liu
    • Dexian Zheng
  • View Affiliations

  • Published online on: January 1, 2008     https://doi.org/10.3892/or.19.1.177
  • Pages: 177-185
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

8-Chloro-adenosine (8-Cl-Ado) is an adenosine derivative, which inhibits proliferation and induces apoptosis in various tumor cells. Subtoxic concentration of 8-Cl-Ado sensitizes human hepatoma cells to tumor necrosis factor-related apoptosis inducing ligand (TRAIL)-triggered apoptosis. However, the molecular mechanism by which TRAIL cytotoxicity is amplified by 8-Cl-Ado is unknown. In the present study, we demonstrated by Western blot and real-time PCR that 8-Cl-Ado selectively up-regulated death receptor 5 (DR5), but not death receptor 4 (DR4), at both protein and RNA levels in human hepatoma cell line BEL-7402. Analysis of the transcriptional regulation of DR5 expression by using Dual-Luciferase reporter assay system demonstrated that the 5'-flanking fragment −207 to −145 upstream to the ATG site within the DR5 promoter region was responsible for the 8-Cl-Ado-upregulated DR5 expression. Electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) confirmed that 8-Cl-Ado treatment facilitated transcription factor Sp1 binding to its cis-element −198/−189 in the DR5 promoter, suggesting that Sp1 is at least one of the 8-Cl-Ado-responsive transcription factors. However, we observed that nuclear factor κB (NF-κB) activity remained invariable in the cells treated with 8-Cl-Ado. These data allowed us to draw a conclusion that 8-Cl-Ado-enhanced DR5 expression is regulated by Sp1 binding to the −198/−189 cis-element in DR5 promoter without affecting NF-κB activity in the hepatoma cells. This study may shed light on further screening the regulators of DR5 expression and developing novel therapeutic drugs for liver cancer.

Related Articles

Journal Cover

January 2008
Volume 19 Issue 1

Print ISSN: 1021-335X
Online ISSN:1791-2431

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Sun M, Zhang J, Liu S, Liu Y and Zheng D: Sp1 is involved in 8-chloro-adenosine-upregulated death receptor 5 expression in human hepatoma cells. Oncol Rep 19: 177-185, 2008
APA
Sun, M., Zhang, J., Liu, S., Liu, Y., & Zheng, D. (2008). Sp1 is involved in 8-chloro-adenosine-upregulated death receptor 5 expression in human hepatoma cells. Oncology Reports, 19, 177-185. https://doi.org/10.3892/or.19.1.177
MLA
Sun, M., Zhang, J., Liu, S., Liu, Y., Zheng, D."Sp1 is involved in 8-chloro-adenosine-upregulated death receptor 5 expression in human hepatoma cells". Oncology Reports 19.1 (2008): 177-185.
Chicago
Sun, M., Zhang, J., Liu, S., Liu, Y., Zheng, D."Sp1 is involved in 8-chloro-adenosine-upregulated death receptor 5 expression in human hepatoma cells". Oncology Reports 19, no. 1 (2008): 177-185. https://doi.org/10.3892/or.19.1.177