近日,，IMIM研究所的研究人員證實乳腺癌細(xì)胞中14-3-3蛋白sigma與腫瘤細(xì)胞激活NF-kB蛋白復(fù)合物的能力有直接聯(lián)系,，NF-kB的激活關(guān)系到腫瘤進(jìn)展。腫瘤中NF-kB的活化情況也被確定為乳腺癌患者復(fù)發(fā)的最佳指標(biāo),。研究人員還介紹了一組乳腺癌細(xì)胞中以及其他,；類型腫瘤細(xì)胞中被激活的于腫瘤預(yù)后較差相關(guān)的基因。
早期研究發(fā)現(xiàn)14-3-3蛋白sigma不存在于許多乳腺癌患者體內(nèi)?，F(xiàn)在研究發(fā)現(xiàn)這種蛋白質(zhì)的缺乏并不是這些類型癌癥的預(yù)后因素之一,，雖然14-3-3蛋白sigma 為NF-kB的保持長期保持活化狀態(tài)，進(jìn)而促進(jìn)腫瘤浸潤和轉(zhuǎn)移是必須的,。
在西方國家,，乳腺癌是最常見的婦女患癌類型，其復(fù)發(fā)和轉(zhuǎn)移是本病的致命結(jié)果,。參與該項研究的約100名患者體內(nèi)都缺乏14-3-3 sigma蛋白,，或許該蛋白可以作為預(yù)后和診斷的一個重要指標(biāo),。
研究人員表示在以后的研究中將逐步確定能誘導(dǎo)14-3-3蛋白在乳腺腫瘤組織中表達(dá)的藥物，14-3-3蛋白sigma可能是將來研究治療靶點中的重要成員,。（生物谷：Bioon.com）
doi:10.1371/journal.pone.0038347
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Inhibition of Specific NF-κB Activity Contributes to the Tumor Suppressor Function of 14-3-3σ in Breast" Cancer
Julia Inglés-Esteve, Mònica Morales, Alba Dalmases, Ricard Garcia-Carbonell, Alba Jené-Sanz, Núria López-Bigas, Mar Iglesias, Cristina Ruiz-Herguido, Ana Rovira, Federico Rojo, Joan Albanell, Roger R. Gomis, Anna Bigas, and Lluís Espinosa.
14-3-3σ is frequently lost in human breast cancers by genetic deletion or promoter methylation. We have now investigated the involvement of 14-3-3σ in the termination of NF-κB signal in mammary cells and its putative role in cancer relapse and metastasis. Our results show that 14-3-3σ regulates nuclear export of p65-NF-κB following chronic TNFα stimulation. Restoration of 14-3-3σ in breast cancer cells reduces migration capacity and metastatic abilities in vivo. By microarray analysis, we have identified a genetic signature that responds to TNFα in a 14-3-3σ-dependent manner and significantly associates with different breast and other types of cancer. By interrogating public databases, we have found that over-expression of this signature correlates with poor relapse-free survival in breast cancer patients. Finally, screening of 96 human breast tumors showed that NF-κB activation strictly correlates with the absence of 14-3-3σ and it is significantly associated with worse prognosis in the multivariate analysis. Our findings identify a genetic signature that is important for breast cancer prognosis and for future personalized treatments based on NF-κB targeting.
