生物谷報道：肺癌（Lung.Carcinoma）是常見的惡性腫瘤之一,，近數(shù)十年肺癌的發(fā)病率和死亡率都有明顯增高的趨勢,。吸煙、被動吸煙,、環(huán)境污染尤其是大氣污染是促成這一嚴峻現(xiàn)實的罪魁禍首,，卻又都是一個長期得不到解決的老大難問題。很多研究顯示,，抽煙與肺癌之間有著緊密的聯(lián)系,，但是具體機制一直沒有弄清,。近日，科學家發(fā)現(xiàn)一種特殊蛋白含量的降低會導致DNA損傷,，從而觸發(fā)肺癌,。這一發(fā)現(xiàn)可能有助于科學家在將來改善對肺癌的治療。
領(lǐng)導此次研究的是美國俄勒岡健康與科學大學癌癥研究所的Laura Hays,。這種特殊的蛋白名為FANCD2，它所在的蛋白質(zhì)家族與遺傳性范可尼貧血癥（Fanconi anemia）有關(guān),，患有此貧血癥的人該家族蛋白含量低,，更易在年輕的時候患癌癥。
研究人員在實驗室中制造了一個人造氣管以模擬抽煙者的肺部環(huán)境,，以此研究了香煙對細胞中不同蛋白的影響,。結(jié)果發(fā)現(xiàn)，當肺細胞暴露于香煙中時,，F(xiàn)ANCD2的制造速度就會變緩,，導致其含量降低。而FANCD2的作用在于通過修補DNA損傷或促進有缺陷細胞自殺來預防癌癥,，所以低水平的FANCD2會導致DNA損傷,，從而觸發(fā)癌癥。
Hays表示,，“這一發(fā)現(xiàn)顯示了FANCD2在保護肺細胞抵御香煙侵襲中扮演著重要角色,，也可能解釋了為什么香煙對肺細胞如此有害。”
論文作者,、美國波特蘭老兵事務醫(yī)學中心的Grover Bagby說：“這一研究顯示了FANCD2是個重要的抵御癌癥蛋白,，而香煙會破壞它的制造過程。雖然這里面還可能包含有其它蛋白,，但我們知道FANCD2是關(guān)鍵的一個,，因為含有非常高水平FANCD2的細胞能夠抵御香煙的毒害作用。”
英國癌癥研究院的Lesley Walker說：“這一研究增加了我們對抽煙致命性原因的理解,。抽煙目前是導致癌癥的最大單一可預防原因,，10例肺癌中有9例都是抽煙所致。不過好消息是,，戒煙是有作用的——戒煙5年后,，心臟病發(fā)作的風險將會降到抽煙者的一半，10年后,，患肺癌的風險同樣也會減半,。”（生物谷www.bioon.com）
生物谷推薦原始出處：
British Journal of Cancer，doi:10.1038/sj.bjc.6604362,，L E Hays,，G C Bagby
Cigarette smoke induces genetic instability in airway epithelial cells by suppressing FANCD2 expression
L E Hays1,2,3, D M Zodrow1,3, J E Yates1,3, M E Deffebach2,3, D B Jacoby2, S B Olson4, J F Pankow5 and G C Bagby1,2,3,4
1OHSU Cancer Institute, Oregon Health & Science University, 3181 Southwest Sam Jackson Park Road, Portland, OR 97239, USA
2Department of Medicine, Oregon Health & Science University, 3181 Southwest Sam Jackson Park Road, Portland, OR 97239, USA
3Veterans Administration Medical Center, 3710 Southwest United States Veteran's Hospital Road, Portland, OR 97239, USA
4Department of Molecular and Medical Genetics, Oregon Health & Science University, 3181 Southwest Sam Jackson Park Road, Portland, OR 97239, USA
5Department of Environmental and Biomolecular Systems, Oregon Graduate Institute, Oregon Health & Science University, 20000 Northwest Walker Road, Beaverton, OR 97006, USA
Chromosomal abnormalities are commonly found in bronchogenic carcinoma cells, but the molecular causes of chromosomal instability (CIN) and their relationship to cigarette smoke has not been defined. Because the Fanconi anaemia (FA)/BRCA pathway is essential for maintenance of chromosomal stability, we tested the hypothesis that cigarette smoke suppresses that activity of this pathway. Here, we show that cigarette smoke condensate (CSC) inhibited translation of FANCD2 mRNA (but not FANCC or FANCG) in normal airway epithelial cells and that this suppression of FANCD2 expression was sufficient to induce both genetic instability and programmed cell death in the exposed cell population. Cigarette smoke condensate also suppressed FANCD2 function and induced CIN in bronchogenic carcinoma cells, but these cells were resistant to CSC-induced apoptosis relative to normal airway epithelial cells. We, therefore, suggest that CSC exerts pressure on airway epithelial cells that results in selection and emergence of genetically unstable somatic mutant clones that may have lost the capacity to effectively execute an apoptotic programme. Carcinogen-mediated suppression of FANCD2 gene expression provides a plausible molecular mechanism for CIN in bronchogenic carcinogenesis.
