来自美国冷泉港实验室（Cold Spring Harbor Lab CSHL）的科学家最近发现了3个新的肺癌致癌基因，它们和20%的肺癌有关。这些基因位于人类14号染色体上，它们彼此相邻，科学家已知其中两个与胎儿期间肺部发育相关。
CSHL的首席科学家David Mu表示：“成人体内的肺癌细胞能使通常只在早期肺部发育过程中活跃的基因恢复活性。我们找到了触发这种异常的发育基因再活跃的变异，并发现如果关闭这些基因就能阻止癌症发展。”
CSHL的科学家发现这3个被称为TTF1、NKX2-8和PAX9的基因能再激发一种早期的胎儿基因表达模式，这会导致肿瘤生长。CSHL科学家，文章合作者Scott Powers说：“3个基因的共同作用以及它们在染色体上如此接近的事实或许能解释该变异为何在肺癌中如此普遍。”通过和Memorial Sloan Kettering肿瘤中心的William Gerald博士合作，研究小组发现这一变异在晚期肺癌中更常见，并有可能是癌症复发的危险因子。
CSHL领导进行的研究证明，该变异导致的癌症是可以逆转的。未来这可能带来新的治疗手段。目前癌症研究只针对单个基因，而事实上癌症通常是由多个肿瘤基因联合造成的。这些基因的变异决定了癌细胞的生长以及癌症治疗的效果。（教育部科技发展中心 ）
原文链接：http://www.physorg.com/news111083679.html
原始出处:
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
