Novel and natural knockout lung cancer cell lines for the LKB1/STK11 tumor suppressor gene
Novel and natural knockout lung cancer cell lines for the LKB1/STK11 tumor suppressor gene
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DOI：
10.1038/sj.onc.1207502
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发表时间：
2004-05-13
期刊：
影响因子：
8
通讯作者：
Sanchez-Cespedes, M
中科院分区：
文献类型：
--
作者：
Carretero, J;Medina, PP;Sanchez-Cespedes, M
LKB 1基因的种系突变导致Peutz-Jeghers综合征（PJS），这是一种常染色体显性遗传疾病，可增加患癌症的风险。我们最近证实LKB 1失活突变不仅限于PJS，也出现在散发性肺腺癌中，包括原发性肿瘤和肺癌细胞系。为了准确地确定肺肿瘤中失活LKB 1基因突变的频率，我们对另外21个肺癌细胞系中LKB 1的完整编码区进行了测序。本文报道了30个不同组织病理类型肺癌细胞系中LKB 1基因的突变情况，其中包括11个肺腺癌（LAD）和11个小细胞肺癌（SCLC）。LKB 1基因改变存在于六个（54%）的LAD细胞系测试，但在其他组织学类型。与我们之前在原发性肿瘤中的观察结果相似，所有点突变都是无义或移码类型，导致异常的截短蛋白质。此外，2个细胞系（A427和H2126）具有跨越多个外显子的大基因缺失。因此，我们已经确定了额外的肺癌细胞系携带失活突变的LKB 1肿瘤抑制基因，进一步证明了该基因在LAD的发展中的重要性，并提供了新的天然LKB 1敲除的LKB 1蛋白的生物学功能的研究。
Germline mutations of the LKB1 gene are responsible for Peutz-Jeghers syndrome (PJS), an autosomal dominant inherited disorder bestowing an increased risk of cancer. We have recently demonstrated that LKB1 inactivating mutations are not confined to PJS, but also appear in lung adenocarcinomas of sporadic origin, including primary tumors and lung cancer cell lines. To accurately determine the frequency of inactivating LKB1 gene mutations in lung tumors we have sequenced the complete coding region of LKB1 in 21 additional lung cancer cell lines. Here we describe the mutational status of LKB1 gene in 30 lung cancer cell lines from different histopathological types, including 11 lung adenocarcinomas (LADs) and 11 small cell lung cancers (SCLCs). LKB1 gene alterations were present in six (54%) of the LAD cell lines tested but in none of the other histological types. Similar to our previous observations in primary tumors, all point mutations were of the nonsense or frameshift type, leading to an abnormal, truncated protein. Moreover, 2 cell lines (A427 and H2126) harbored large gene deletions that spanned several exons. Hence, we have identified additional lung cancer cell lines carrying inactivating mutations of the LKB1 tumor suppressor gene, further attesting to the significance of this gene in the development of LADs and providing new natural LKB1 knockouts for studies of the biological function of the LKB1 protein.