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PRL-3 promotes the proliferation of LoVo cells via the upregulation of KCNN4 channels.

Abstract
Previous studies have shown that phosphatase of regenerating liver-3 (PRL-3) plays an important role in the metastasis and proliferation of tumor cells. However, the mechanism by which PRL-3 controls the cell cycle of tumor cells remains unknown. In the present study, considering that the K+ channels strictly control cell proliferation, we examined whether K+ channels participate in the proliferation of tumor cells induced by PRL-3. Interestingly, the expression of intermediate-conductance Ca2+-activated K+ channels (KCNN4) was upregulated in an NF-κB-dependent manner when PRL-3 was transfected into LoVo cells. Also, we identified two NF-κB binding sites in the promoter region of KCNN4. Use of the specific inhibitor 1-[(2-chlorophenyl) diphenylmethyl]-1H-pyrazole (TRAM-34) significantly inhibited the proliferation induced by PRL-3 and blocked the cell cycle at the G2/M phase. Meanwhile, the level of phosphorylation of Cdc2 was increased in a dose-dependent manner. Furthermore, TRAM-34 also inhibited tumor formation of PRL-3 cell xenografts implanted by injection in nude mice. In conclusion, PRL-3 promoted the proliferation of LoVo cells through upregulation of KCNN4 channels which facilitated the G2/M transition.
AuthorsWei Lai, Shuang Chen, Heng Wu, Yufeng Guan, Lu Liu, Yujie Zeng, Haiyan Zhao, Jianmin Jiang, Zhonghua Chu
JournalOncology reports (Oncol Rep) Vol. 26 Issue 4 Pg. 909-17 (Oct 2011) ISSN: 1791-2431 [Electronic] Greece
PMID21725609 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Intermediate-Conductance Calcium-Activated Potassium Channels
  • KCNN4 protein, human
  • Neoplasm Proteins
  • Pyrazoles
  • TRAM 34
  • PTP4A3 protein, human
  • Protein Tyrosine Phosphatases
Topics
  • Animals
  • Cell Division (physiology)
  • Cell Growth Processes (physiology)
  • Cell Line, Tumor
  • Colonic Neoplasms (genetics, metabolism, pathology)
  • Female
  • G2 Phase (physiology)
  • Humans
  • Intermediate-Conductance Calcium-Activated Potassium Channels (antagonists & inhibitors, genetics, metabolism)
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasm Proteins (antagonists & inhibitors, biosynthesis, genetics, metabolism)
  • Protein Tyrosine Phosphatases (antagonists & inhibitors, biosynthesis, genetics, metabolism)
  • Pyrazoles (pharmacology)
  • Transfection
  • Up-Regulation

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