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.
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Authors | Wei Lai, Shuang Chen, Heng Wu, Yufeng Guan, Lu Liu, Yujie Zeng, Haiyan Zhao, Jianmin Jiang, Zhonghua Chu |
Journal | Oncology reports
(Oncol Rep)
Vol. 26
Issue 4
Pg. 909-17
(Oct 2011)
ISSN: 1791-2431 [Electronic] Greece |
PMID | 21725609
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Intermediate-Conductance Calcium-Activated Potassium Channels
- KCNN4 protein, human
- Neoplasm Proteins
- Pyrazoles
- TRAM 34
- PTP4A3 protein, human
- Protein Tyrosine Phosphatases
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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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