Genetic and epigenetic inactivation of LTF gene at 3p21.3 in lung cancers
Genetic and epigenetic inactivation of LTF gene at 3p21.3 in lung cancers
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DOI：
10.1002/ijc.21462
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发表时间：
2006-02-15
影响因子：
6.4
通讯作者：
Mori, M
中科院分区：
文献类型：
--
作者：
Iijima, H;Tomizawa, Y;Mori, M
3 号染色体短臂上的等位基因丢失是肺癌发病机制中最常见的事件之一。乳转铁蛋白基因（LTF，也称为乳铁蛋白基因，LF）位于3p21.3共同消除区域1，该区域在肺癌和其他癌症中经常被删除。 LTF基因在27个小细胞肺癌细胞系中的16个（59%）、43个非小细胞肺癌（NSCLC）细胞系中的33个（77%）和13个原发性NSCLC细胞系中的7个（54%）中缺失，而LTF mRNA在43个NSCLC细胞系中的3个（7%）中过表达。在不表达 LTF 的肺癌细胞系子集中，用 5-aza-2'-脱氧胞苷 (5-aza-dC)、曲古抑菌素 A (TSA) 或两者的组合治疗可恢复其表达。此外，我们还发现了 8 种不同类型的核苷酸取代和一种移码突变。这些结果表明 LTF 基因在肺癌中通过遗传和表观遗传机制失活。 (c) 2005 年 Wiley-Liss, Inc.
Allelic loss on the short arm of chromosome 3 is one of the most common events in the pathogenesis of lung cancer. The lactotransferrin gene (LTF, also referred to as the lactoferrin gene, LF) is located at 3p21.3 common eliminated region 1, which is frequently deleted in lung and other cancers. The expression of the LTF gene was absent in 16 (59%) of 27 small cell lung cancer cell lines, 33 (77%) of 43 nonsmall-cell lung cancer (NSCLC) cell lines and 7 (54%) of 13 primary NSCLC, while LTF mRNA was overexpressed in 3 (7%) of 43 NSCLC cell lines. Its expression was restored by treatment with 5-aza-2'-deoxycytidine (5-aza-dC), trichostatin A (TSA) or a combination of both in a subset of lung cancer cell lines without LTF expression. In addition, we found 8 different types of nucleotide substitutions and one frameshift mutation. These results indicate that the LTF gene is inactivated by genetic and epigenetic mechanisms in lung cancer. (c) 2005 Wiley-Liss, Inc.