Establishment and expression profiling of new lung cancer cell lines from Chinese smokers and lifetime never-smokers
Establishment and expression profiling of new lung cancer cell lines from Chinese smokers and lifetime never-smokers
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DOI：
10.1097/01243894-200611000-00003
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发表时间：
2006-11-01
影响因子：
20.4
通讯作者：
Wong, Maria P.
中科院分区：
文献类型：
--
作者：
Lam, David C. L.;Girard, Luc;Wong, Maria P.
背景资料：支气管腺癌是肺癌的主要组织学亚型，在男性和女性癌症死亡率中均居首位。近几十年来，女性非吸烟者和腺癌在肺癌患者中已成为一种独特的组合。肺癌细胞系建立从已知的临床特征，如性别和吸烟习惯的患者将是有用的，为未来的研究对lung cancer.Methods：四个新的肺腺癌细胞系（HKULC 1-4）建立从中国原发性肺腺癌患者和不同的临床特征，年龄，性别，吸烟习惯，肿瘤分期，和以前的治疗。通过免疫组化和生长动力学研究、裸鼠致瘤性试验、表皮生长因子受体（EGFR）基因突变分析、原位杂交和Affyphase基因芯片HG-U133 A的基因表达谱分析对其进行表征。新建立的HKULC肺腺癌细胞系可传代70代以上，并显示出形态学和免疫组化特征以及生长动力学特征。肿瘤细胞系四个HKULC细胞系之一，HKULC 3（来自一名女性非吸烟肺腺癌患者），被发现有EGFR基因外显子19的缺失。EGFR原位杂交显示这些细胞系中没有EGFR基因扩增。HKULC 1和4在裸鼠中接种后形成肿瘤异种移植物。鉴定了差异表达或显示类别预测意义的71个基因的列表。这些基因包括假定的肿瘤抑制基因（DKK 3、SERPINF 1、CDH 11、DSC 3和KLF 6），参与EGFR途径或与EGFR途径相关的基因（ERBB 3、MUC 1、VAV 1），参与细胞周期和增殖调节的基因（CDKN 1A和CDKN 2A），一个假定的致癌基因（EEF 1A 2），和一个与转移相关的基因（MTSS 1）。从具有不同临床特征的患者中建立了四种新的肺腺癌细胞系。这些特征性细胞系及其基因表达谱将为肺癌生物学研究和体外化疗药物研究提供资源。
Background: Bronchogenic adenocarcinoma is the predominant histologic subtype of lung cancer, which ranks top in the cancer mortality in both men and women. Female nonsmokers and adenocarcinoma have emerged as a distinct combination in patients with lung cancer in recent decades. Lung cancer cell lines established from patients with known clinical characteristics such as gender and smoking habit would be useful for future research on lung cancer.Methods: Four new lung adenocarcinoma cell lines (HKULC 1-4) were established from Chinese patients with primary lung adenocarcinomas and with different clinical characteristics with respect to age, gender, smoking habits, tumor staging, and previous therapy. They were characterized by immunohistochemical and growth kinetic studies, tests for tumorigenicity in nude mice, epidermal growth factor receptor (EGFR) gene mutation analysis, and in situ hybridization, and gene expression profiling with Affymetrix Gene-Chip HG-U133A.Results: The newly established HKULC lung adenocarcinoma cell lines were maintained for over 70 passages and demonstrated morphologic and immunohistochemical features and growth kinetics of tumor cell lines. One of the four HKULC cell lines, HKULC 3 (derived from a female nonsmoking patient with lung adenocarcinoma), was found to have a deletion at exon 19 of the EGFR gene. EGFR in situ hybridization showed no EGFR gene amplification in these cell lines. HKULC 1 and 4 formed tumor xenografts after inoculation in nude mice. A list of 71 genes that were differentially expressed or showing class predictive significance was identified. These genes included putative tumor suppressor genes (DKK3, SERPINF1, CDH11, DSC3, and KLF6), genes involved in or related to the EGFR pathways (ERBB3, MUC1, VAV1), genes involved in regulation of cell cycle and proliferation (CDKN1A and CDKN2A), a putative oncogene (EEF1A2), and a gene related to metastasis (MTSS1).Discussion: Four new lung adenocarcinoma cell lines were established from patients with different clinical characteristics. These characterized cell lines and their gene expression profiles will provide resources for studies of lung cancer biology and in vitro chemotherapeutic drug study.