PRL-3 promotes the proliferation of LoVo cells via the upregulation of KCNN4 channels
PRL-3 promotes the proliferation of LoVo cells via the upregulation of KCNN4 channels
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DOI：
10.3892/or.2011.1366
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发表时间：
2011-10-01
期刊：
影响因子：
4.2
通讯作者：
Chu, Zhonghua
中科院分区：
文献类型：
--
作者：
Lai, Wei;Chen, Shuang;Chu, Zhonghua
以往的研究表明，肝再生磷酸酶-3（PRL-3）在肿瘤细胞的转移和增殖中起重要作用。然而，PRL-3控制肿瘤细胞的细胞周期的机制仍然未知。在本研究中，考虑到K+通道严格控制细胞增殖，我们研究了K+通道是否参与PRL-3诱导的肿瘤细胞增殖。有趣的是，当PRL-3转染到LoVo细胞中时，中电导Ca 2+激活的K+通道（KCNN 4）的表达以NF-κ B依赖的方式上调。此外，我们确定了两个NF-κ B B结合位点的启动子区的KCNN 4。使用特异性抑制剂1-[（2-氯苯基）二苯基甲基]-1H-吡唑（TRAM-34）可显著抑制PRL-3诱导的细胞增殖，并将细胞周期阻滞在G2/M期。同时，Cdc 2的磷酸化水平呈剂量依赖性增加。此外，TRAM-34还抑制通过注射植入裸鼠的PRL-3细胞异种移植物的肿瘤形成。结论：PRL-3通过上调KCNN 4通道促进LoVo细胞的增殖，促进细胞G2/M期转换。
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-kappa B-dependent manner when PRL-3 was transfected into LoVo cells. Also, we identified two NF-kappa B 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.