Change in gene expression profiles of secreted frizzled-related proteins (SFRPs) by sodium butyrate in gastric cancers: Induction of promoter demethylation and histone modification causing inhibition of Wnt signaling

  • Authors:
    • Hyunsoo Shin
    • Jie-Hyun Kim
    • Yeo Song Lee
    • Yong Chan Lee
  • View Affiliations

  • Published online on: January 10, 2012     https://doi.org/10.3892/ijo.2012.1327
  • Pages: 1533-1542
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Abstract

Activation of Wnt signaling without mutation of β-catenin or APC occurs frequently in human gastric cancers. Secreted frizzled-related protein (SFRP), a negative modulator of the Wnt signaling pathway, are frequently inactivated in human gastric cancers. Inhibition of SFRP gene expression may account for the Wnt/β-catenin activation in human gastric cancer. However, the molecular mechanisms of silencing of SFRP genes are not fully understood. Sodium butyrate, a histone deacetylase (HDAC) inhibitor, is known to exhibit anti-cancer effects partly through the differentiation of various cancer cells. In the present study, we investigated: i) the relationship between the silencing of SFRP genes and Wnt signaling; ii) the mechanism of sodium butyrate mediated epigenetic regulation of SFRPs expression in human gastric cancer. We observed that nuclear β-catenin was significantly increased in gastric cancer tissues as compared to adjacent non-cancerous tissues. Nuclear β-catenin accumulation and SFRP promoter methylation in human gastric cancer cells were noted. Treatment with the DNA methyltransferase inhibitor, 5'-Aza-2-deoxycytidine (5'-Aza-dC) rapidly restored SFRPs expression. Sodium butyrate (NaB) induced demethylation and histone modification at the promoter region of SFRP1/2 restoring the SFRP expression in human gastric cancer cells. Analysis of general expression revealed that overexpression of SFRPs repressed Wnt target gene expression and induced changes in the proliferation and apoptosis related genes in human gastric cancer cells. These data suggest that aberrant epigenetic modification of SFRP genes is one of the major mechanisms by which Wnt signaling is activated in human gastric cancer cells and sodium butyrate may modulate the SFRP1/2 expression through histone modification and promoter demethylation causing anti-tumor effects.

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May 2012
Volume 40 Issue 5

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Shin H, Kim J, Lee YS and Lee YC: Change in gene expression profiles of secreted frizzled-related proteins (SFRPs) by sodium butyrate in gastric cancers: Induction of promoter demethylation and histone modification causing inhibition of Wnt signaling. Int J Oncol 40: 1533-1542, 2012.
APA
Shin, H., Kim, J., Lee, Y.S., & Lee, Y.C. (2012). Change in gene expression profiles of secreted frizzled-related proteins (SFRPs) by sodium butyrate in gastric cancers: Induction of promoter demethylation and histone modification causing inhibition of Wnt signaling. International Journal of Oncology, 40, 1533-1542. https://doi.org/10.3892/ijo.2012.1327
MLA
Shin, H., Kim, J., Lee, Y. S., Lee, Y. C."Change in gene expression profiles of secreted frizzled-related proteins (SFRPs) by sodium butyrate in gastric cancers: Induction of promoter demethylation and histone modification causing inhibition of Wnt signaling". International Journal of Oncology 40.5 (2012): 1533-1542.
Chicago
Shin, H., Kim, J., Lee, Y. S., Lee, Y. C."Change in gene expression profiles of secreted frizzled-related proteins (SFRPs) by sodium butyrate in gastric cancers: Induction of promoter demethylation and histone modification causing inhibition of Wnt signaling". International Journal of Oncology 40, no. 5 (2012): 1533-1542. https://doi.org/10.3892/ijo.2012.1327