Nuclear envelope component PRR14 has been detected to be upregulated in varieties of cancers, especially in breast cancer. But its role in breast carcinogenesis is poorly understood. In this study, we show PRR14 contributes to breast carcinogenesis mainly through overexpression, which derives from elevated transcription and gene amplification. Increased PRR14 expression promotes breast cancer cell proliferation and tumor formation. Biochemical analysis reveals, in addition to previously reported activation of PI3-kinase/Akt/mTOR pathway, PRR14 overexpression regulates cell cycle in breast cancer by inhibiting CHEK2’s activation, followed with the deregulation of DNA damage pathway. In correspondence, CHEK2 and PRR14 show opposite impact on breast cancer patients receiving chemotherapy. Collectively, our study is the first to document the oncogenetic role of PRR14 in breast cancer, which protects cells from apoptosis and stimulates proliferation by activating the PI3-kinase/Akt/mTOR pathway and inhibiting the CHEK2 pathway. Both of these pathways are of great influence in breast cancer and PRR14 appears to be their novel interacting node, which renders patients more resistance to chemotherapy and provides a potential therapeutic target in breast cancer.

已发现核包膜成分PRR14在多种癌症中，特别是在乳腺癌中被上调。但是，其在乳腺癌致癌作用中的作用知之甚少。在这项研究中，我们显示PRR14主要通过过度表达来促进乳腺癌的发生，过度表达是由于转录和基因扩增升高所致。PRR14表达增加会促进乳腺癌细胞增殖和肿瘤形成。生化分析表明，除先前报道的PI3-激酶/ Akt / mTOR途径激活外，PRR14过表达还通过抑制CHEK2的激活来调节乳腺癌细胞的周期，随后解除DNA损伤途径的调控。相应地，CHEK2和PRR14对接受化疗的乳腺癌患者显示出相反的影响。总的来说，乳腺癌中的PRR14通过激活PI3-激酶/ Akt / mTOR通路并抑制CHEK2通路来保护细胞免于凋亡并刺激增殖。这两种途径在乳腺癌中均具有重大影响，PRR14似乎是它们的新型相互作用节点，这使患者对化学疗法更具抵抗力，并为乳腺癌提供了潜在的治疗靶标。