14-3-3σ is down-regulated in human prostate cancer

Tomohiko Urano, Satoru Takahashi, Takashi Suzuki, Tetsuya Fujimura, Masayo Fujita, Jinpei Kumagai, Kuniko Horie-Inoue, Hironobu Sasano, Tadaichi Kitamura, Yasuyoshi Ouchi, Satoshi Inoue

Research output: Contribution to journalArticlepeer-review

35 Citations (Scopus)

Abstract

The 14-3-3σ is a negative regulator of the cell cycle, which is induced by p53 in response to DNA damage. It has been characterized as an epithelium-specific marker and down-regulation of the protein has been shown in breast cancers, suggesting its tumor-suppressive activity in epithelial cells. Here we demonstrate that 14-3-3σ protein is down-regulated in human prostate cancer cell lines, LNCaP, PC3, and DU145 compared with normal prostate epithelial cells. Immunohistochemical analysis of primary prostate cells shows that the expression of 14-3-3σ protein is epithelial cell-specific. Among prostate pathological specimens, >95% of benign hyperplasia samples show significant and diffuse immunostaining of 14-3-3σ in the cytoplasm whereas <20% of carcinoma samples show positive staining. In terms of mechanisms for the down-regulation of 14-3-3σ in prostate cancer cells, hypermethylation of the gene promoter plays a causal role in LNCaP cells as 14-3-3σ mRNA level was elevated by 5-aza-2-deoxycytidine demethylating treatment. Intriguingly, the proteasome-mediated proteolysis is responsible for 14-3-3σ reduction in DU145 and PC3 cells, as 14-3-3σ protein expression was increased by treatment with a proteasome inhibitor MG132. Furthermore, tumor necrosis factor-related apoptosis-inducing ligand enhances 14-3-3σ gene and protein expression in DU145 and PC3 cells. These data suggest that 14-3-3σ expression is down-regulated during the neoplastic transition of prostate epithelial cells.

Original languageEnglish
Pages (from-to)795-800
Number of pages6
JournalBiochemical and biophysical research communications
Volume319
Issue number3
DOIs
Publication statusPublished - 2004 Jul 2

Keywords

  • 14-3-3σ
  • Cell cycle
  • Epithelial cells
  • Methylation
  • Prostate cancer
  • Proteasome
  • Tumor necrosis factor-related apoptosis-inducing ligand

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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