NES1/KLK10 gene represses proliferation, enhances apoptosis and down-regulates glucose metabolism of PC3 prostate cancer cells.
NES1/KLK10 gene represses proliferation, enhances apoptosis and down-regulates glucose metabolism of PC3 prostate cancer cells.
复制标题
NES1/KLK10 基因抑制 PC3 前列腺癌细胞的增殖、增强细胞凋亡并下调葡萄糖代谢。
DOI：
10.1038/srep17426
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发表时间：
2015-11-30
影响因子：
4.6
通讯作者：
Li B
中科院分区：
文献类型：
--
作者：
Hu J;Lei H;Fei X;Liang S;Xu H;Qin D;Wang Y;Wu Y;Li B
正常上皮细胞特异性1（NES 1）基因，也被称为KLK 10，被认为是乳腺癌中一种新的肿瘤抑制因子，但很少有研究集中在人前列腺癌中KLK 10的功能。我们的研究证实，KLK 10在前列腺癌组织和细胞系（PC 3、DU 145和LNCaP克隆FGC）中的表达较低。考虑到PC 3细胞系的雄激素非依赖性生长特征与临床去势抵抗性前列腺癌更相似，我们研究了KLK 10在PC 3中的作用。体外和体内实验表明，在PC 3中过表达KLK 10可以减缓肿瘤增殖，这伴随着细胞凋亡的增加和葡萄糖代谢的抑制。相关蛋白Bcl-2、HK-2表达下调。此外，通过上调Bcl-2或HK-2分别在PC 3-KLK 10细胞系中，我们观察到随后的细胞增殖的增加和HK-2和Bcl-2的同步上调。此外，Bcl-2和HK-2还能促进KLK 10的表达，提示KLK 10与Bcl-2/HK-2之间存在负反馈环。因此，我们的研究结果表明，KLK 10可能作为一种肿瘤抑制剂，抑制增殖，促进细胞凋亡和降低葡萄糖代谢的PC 3细胞。
The normal epithelial cell-specific-1 (NES1) gene, also named as KLK10, is recognised as a novel putative tumour suppressor in breast cancer, but few studies have focused on the function of KLK10 in human prostate cancer. Our study confirms that the expression of KLK10 in prostate cancer tissue and cell lines (PC3, DU145, and LNCaP clone FGC) is low. Given that the androgen-independent growth characteristic of the PC3 cell line is more similar to clinical castration-resistant prostate cancer, we studied the role of KLK10 in PC3. In vitro and in vivo assays showed that over-expressing KLK10 in PC3 could decelerate tumour proliferation, which was accompanied with an increase in apoptosis and suppression of glucose metabolism. The related proteins, such as Bcl-2 and HK-2, were down-regulated subsequently. Furthermore, by up-regulating Bcl-2 or HK-2 respectively in the PC3-KLK10 cell line, we observed a subsequent increase of cell proliferation and a synchronous up-regulation of HK-2 and Bcl-2. Besides, KLK10 expression was also increased by Bcl-2 and HK-2, which suggests that there is a negative feedback loop between KLK10 and Bcl-2/HK-2. Thus, our results demonstrated that KLK10 may function as a tumour suppressor by repressing proliferation, enhancing apoptosis and decreasing glucose metabolism in PC3 cells.