近日,，美國(guó)弗吉尼亞聯(lián)邦大學(xué)科學(xué)家發(fā)現(xiàn)了一種稱(chēng)為SARI的新抑癌基因,，它能夠參與并抑制一種關(guān)鍵蛋白質(zhì),，這種蛋白質(zhì)在90%的人類(lèi)癌癥中都過(guò)度表達(dá),。這一發(fā)現(xiàn)有可能幫助科學(xué)家開(kāi)發(fā)出有效的癌癥基因療法,。相關(guān)研究論文12月8日在線發(fā)表于美國(guó)《國(guó)家科學(xué)院院刊》（PNAS）,。
研究人員用一種Fisher實(shí)驗(yàn)室開(kāi)發(fā)的,、稱(chēng)為差減雜交(Subtraction hybridization)的技術(shù)發(fā)現(xiàn)了這種新抑癌基因SARI。它通過(guò)干擾癌細(xì)胞分子的作用,，抑制腫瘤的生長(zhǎng)和存活,。
研究人員將SARI遞送到癌癥細(xì)胞，癌細(xì)胞會(huì)停止分裂并死亡,。由于90%的癌癥種類(lèi)都基于相似的機(jī)制來(lái)存活和生長(zhǎng),，所以，F(xiàn)isher表示,，SARI可能成為多種癌癥的有效療法,。
根據(jù)弗吉尼亞聯(lián)邦大學(xué)教授,、該項(xiàng)目首席研究員Paul B. Fisher的說(shuō)法，這一新發(fā)現(xiàn)的基因揭示出一種先前未認(rèn)識(shí)到的分子通路,，這種通路與干擾素INF抗腫瘤作用有關(guān),。
Fisher表示：“IFN是強(qiáng)大的免疫調(diào)制劑，有助于對(duì)癌癥的免疫應(yīng)答,，而且是新血管形成有效的抑制劑,。在原發(fā)和轉(zhuǎn)移癌癥的發(fā)展中，血管形成都是必須的,。”
Fisher說(shuō)：“我們揭示了干擾素引發(fā)抑癌活動(dòng)的新手段,。SARI的發(fā)現(xiàn)也提供了一種新的潛在的反應(yīng)物，可以選擇性地殺死腫瘤細(xì)胞,。”
研究小組目前正致力于改進(jìn)方法,，以更有效地標(biāo)靶SARI的遞送。Fisher表示,，這些研究對(duì)于探究這一基因的癌癥選擇性殺傷活性并增強(qiáng)它的治療性應(yīng)用至關(guān)重要,。（生物谷Bioon.com）
生物谷推薦原始出處：
PNAS，DOI: 10.1073/pnas.0807975106,， Zao-zhong Su,，Paul B. Fisher
Cloning and characterization of SARI (suppressor of AP-1, regulated by IFN)
Zao-zhong Su, Seok-Geun Lee, Luni Emdada, Irina V. Lebdeva, Pankaj Gupta, Kristoffer Valerie, Devanand Sarkar, and Paul B. Fisher
Abstract
We describe a novel basic leucine zipper containing type I IFN-inducible early response gene SARI (Suppressor of AP-1, Regulated by IFN). Steady-state SARI mRNA expression was detected in multiple lineage-specific normal cells, but not in their transformed/tumorigenic counterparts. In normal and cancer cells, SARI expression was induced 2 h after fibroblast IFN (IFN-β) treatment with 1 U/ml of IFN-β. Antisense inhibition of SARI protected HeLa cells from IFN-β-mediated growth inhibition. As a corollary, overexpression of SARI inhibited growth and induced apoptosis in cancer cells, but not in normal cells. SARI interacted with c-Jun via its leucine zipper, resulting in inhibition of DNA binding of activator protein (AP-1) complex and consequently AP-1-dependent gene expression. Transformed cells relying on AP-1 activity for proliferative advantage demonstrated increased susceptibility to SARI-mediated growth inhibition. These findings uncover a novel mode of IFN-induced anti-tumor growth suppression and suggest potential gene therapy applications for SARI.
