Skp2 is over-expressed in breast cancer and promotes breast cancer cell proliferation.
Skp2 is over-expressed in breast cancer and promotes breast cancer cell proliferation.
复制标题
Skp2在乳腺癌中过度表达并促进乳腺癌细胞增殖。
DOI：
10.1080/15384101.2016.1160986
复制
发表时间：
2016
期刊：
影响因子：
4.3
通讯作者：
Guan Xiaoxiang
中科院分区：
文献类型：
--
作者：
Zhang Wenwen;Cao Lulu;Sun Zijia;Xu Jing;Tang Lin;Chen Weiwei;Luo Jiayan;Yang Fang;Wang Yucai;Guan Xiaoxiang
F盒蛋白Skp2是致癌的。Skp2和Skp2B是Skp2的一个亚型，在乳腺癌中过表达。然而，关于Skp2B促进乳腺癌发生和发展的机制还知之甚少。在此，我们利用乳腺癌数据库检测了Skp2在乳腺癌标本和细胞系中的表达和临床结局，并探讨了Skp2和Skp2B在乳腺癌细胞生长、凋亡和细胞周期停滞中的作用。我们发现Skp2在乳腺癌标本和细胞系中显著过表达，并且Skp2的高表达与乳腺癌的不良预后呈正相关。Skp2和Skp2B均能促进乳腺癌细胞增殖，抑制细胞凋亡，改变细胞周期分布，诱导S期细胞增多，从而诱导乳腺癌细胞增殖。此外，这两种异构体都可以通过独立的途径抑制PIG3在乳腺癌细胞中的表达。Skp2抑制P53并抑制PIG3诱导的细胞凋亡，而Skp2B通过抑制PHB而减弱PIG3的功能。我们的结果表明Skp2和Skp2B诱导乳腺癌细胞的生长和发展，使Skp2和Skp2B成为乳腺癌治疗的潜在分子靶点。
The F box protein Skp2 is oncogenic. Skp2 and Skp2B, an isoform of Skp2 are overexpressed in breast cancer. However, little is known regarding the mechanism by which Skp2B promotes the occurrence and development of breast cancer. Here, we determined the expression and clinical outcomes of Skp2 in breast cancer samples and cell lines using breast cancer database, and investigated the role of Skp2 and Skp2B in breast cancer cell growth, apoptosis and cell cycle arrest. We obtained Skp2 is significantly overexpressed in breast cancer samples and cell lines, and high Skp2 expression positively correlated with poor prognosis of breast cancer. Both Skp2 and Skp2B could promote breast cancer cell proliferation, inhibit cell apoptosis, change the cell cycle distribution and induce the increased S phase cells and therefore induce cell proliferation in breast cancer cells. Moreover, the 2 isoforms could both suppress PIG3 expression via independent pathways in the breast cancer cells. Skp2 suppressed p53 and inhibited PIG3-induced apoptosis, while Skp2B attenuated the function of PIG3 by inhibiting PHB. Our results indicate that Skp2 and Skp2B induce breast cancer cell development and progression, making Skp2 and Skp2B potential molecular targets for breast cancer therapy.