Hong Kyeong-Man, Yang Sei-Hoon, Chowdhuri Sinchita Roy, Player Audrey, Hames Megan, Fukuoka Junya, Meerzaman Daoud, Dracheva Tatiana, Sun Zhifu, Yang Ping, Jen Jin
Laboratory of Population Genetics, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Int J Cancer. 2007 Jun 1;120(11):2353-8. doi: 10.1002/ijc.22577.
Serial analysis of gene expression studies led us to identify a previously unknown gene, c20orf85, that is present in the normal lung epithelium but absent or downregulated in most primary nonsmall cell lung cancers and lung cancer cell lines. We named this gene LLC1 for Low in Lung Cancer 1. LLC1 is located on chromosome 20q13.3 and has a 70% GC content in the promoter region. It has 4 exons and encodes a protein containing 137 amino acids. By in situ hybridization, we observed that LLC1 message is localized in normal lung bronchial epithelial cells but absent in 13 of 14 lung adenocarcinoma and 9 out of 10 lung squamous carcinoma samples. Methylation at CpG sites of the LLC1 promoter was frequently observed in lung cancer cell lines and in a fraction of primary lung cancer tissues. Treatment with 5-aza deoxycytidine resulted in a reduced methylation of the LLC1 promoter concomitant with the increase of LLC1 expression. These results suggest that inactivation of LLC1 by means of promoter methylation is a frequent event in nonsmall cell lung cancer and may play a role in lung tumorigenesis.
基因表达序列分析研究使我们鉴定出一个先前未知的基因c20orf85，该基因存在于正常肺上皮中，但在大多数原发性非小细胞肺癌和肺癌细胞系中缺失或下调。我们将这个基因命名为LLC1，即肺癌中低表达基因1。LLC1位于20号染色体q13.3，其启动子区域的GC含量为70%。它有4个外显子，编码一个含137个氨基酸的蛋白质。通过原位杂交，我们观察到LLC1的信使核糖核酸定位于正常肺支气管上皮细胞，但在14例肺腺癌中的13例以及10例肺鳞癌样本中的9例中缺失。在肺癌细胞系和部分原发性肺癌组织中经常观察到LLC1启动子CpG位点的甲基化。用5-氮杂脱氧胞苷处理导致LLC1启动子甲基化减少，同时LLC1表达增加。这些结果表明，通过启动子甲基化使LLC1失活在非小细胞肺癌中是常见事件，可能在肺肿瘤发生中起作用。
