來自美國冷泉港實驗室（Cold Spring Harbor Lab CSHL）的科學家最近發(fā)現(xiàn)了3個新的肺癌致癌基因,，它們和20%的肺癌有關(guān),。這些基因位于人類14號染色體上,，它們彼此相鄰,，科學家已知其中兩個與胎兒期間肺部發(fā)育相關(guān),。
CSHL的首席科學家David Mu表示：“成人體內(nèi)的肺癌細胞能使通常只在早期肺部發(fā)育過程中活躍的基因恢復活性,。我們找到了觸發(fā)這種異常的發(fā)育基因再活躍的變異,，并發(fā)現(xiàn)如果關(guān)閉這些基因就能阻止癌癥發(fā)展,。”
CSHL的科學家發(fā)現(xiàn)這3個被稱為TTF1、NKX2-8和PAX9的基因能再激發(fā)一種早期的胎兒基因表達模式,，這會導致腫瘤生長,。CSHL科學家，文章合作者Scott Powers說：“3個基因的共同作用以及它們在染色體上如此接近的事實或許能解釋該變異為何在肺癌中如此普遍,。”通過和Memorial Sloan Kettering腫瘤中心的William Gerald博士合作,，研究小組發(fā)現(xiàn)這一變異在晚期肺癌中更常見，并有可能是癌癥復發(fā)的危險因子,。
CSHL領(lǐng)導進行的研究證明,，該變異導致的癌癥是可以逆轉(zhuǎn)的。未來這可能帶來新的治療手段,。目前癌癥研究只針對單個基因,，而事實上癌癥通常是由多個腫瘤基因聯(lián)合造成的。這些基因的變異決定了癌細胞的生長以及癌癥治療的效果,。（教育部科技發(fā)展中心 ）
原文鏈接：http://www.physorg.com/news111083679.html
原始出處:
Published online before print October 9, 2007
Proc. Natl. Acad. Sci. USA, 10.1073/pnas.0708286104
MEDICAL SCIENCES
Oncogenic cooperation and coamplification of developmental transcription factor genes in lung cancer
Jude Kendall*, Qing Liu, Amy Bakleh, Alex Krasnitz*, Ken C. Q. Nguyen, B. Lakshmi*, William L. Gerald, Scott Powers*,, and David Mu*,,
*Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724; Cancer Genome Center, Cold Spring Harbor Laboratory, Woodbury, NY 11797; and Memorial Sloan–Kettering Cancer Center, New York, NY 10065
Communicated by Bruce W. Stillman, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, September 4, 2007 (received for review June 21, 2007)
Abstract
We used high-resolution array analysis to discover a recurrent lung cancer amplicon located at 14q13.3. Low-level gain of this region was detected in 15% of lung cancer samples, and high-level amplification was detected in an additional 4% of samples. High-level focal amplification appears to be specific to lung cancers, because it was not detected in >500 samples of other tumor types. Mapping of the commonly amplified region revealed there are three genes in the core region, all of which encode transcription factors with either established lung developmental function (TTF1/NKX2-1, NKX2-8) or potential lung developmental function (PAX9). All three genes were overexpressed to varying degrees in amplified samples, although TTF1/NKX2-1 was not expressed in the squamous cancer subtype, consistent with previous reports. Remarkably, overexpression of any pairwise combination of these genes showed pronounced synergy in promoting the proliferation of immortalized human lung epithelial cells. Analysis of human lung cancer cell lines by both RNAi and ectopic overexpression further substantiates an oncogenic role for these transcription factors. These results, taken together with previous reports of oncogenic alterations of transcription factors involved in lung development (p63, CEBPA), suggest genetic alterations that directly interfere with transcriptional networks normally regulating lung development may be a more common feature of lung cancer than previously realized.
gene amplification | lung development | lung oncogene | TTF1 NKX2-8 PAX9 | lineage addiction
