近日,，美國弗吉尼亞聯(lián)邦大學(xué)科學(xué)家發(fā)現(xiàn)了一種稱為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%的人類癌癥中都過度表達,。這一發(fā)現(xiàn)有可能幫助科學(xué)家開發(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《國家科學(xué)院院刊》（PNAS）,。
研究人員用一種Fisher實驗室開發(fā)的,、稱為差減雜交(Subtraction hybridization)的技術(shù)發(fā)現(xiàn)了這種新抑癌基因SARI。它通過干擾癌細胞分子的作用,，抑制腫瘤的生長和存活,。
研究人員將SARI遞送到癌癥細胞，癌細胞會停止分裂并死亡,。由于90%的癌癥種類都基于相似的機制來存活和生長,，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,、該項目首席研究員Paul B. Fisher的說法,，這一新發(fā)現(xiàn)的基因揭示出一種先前未認識到的分子通路,，這種通路與干擾素INF抗腫瘤作用有關(guān)。
Fisher表示：“IFN是強大的免疫調(diào)制劑,，有助于對癌癥的免疫應(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：“我們揭示了干擾素引發(fā)抑癌活動的新手段。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胞,。”
研究小組目前正致力于改進方法，以更有效地標靶SARI的遞送,。Fisher表示,，這些研究對于探究這一基因的癌癥選擇性殺傷活性并增強它的治療性應(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.
