Lam David C L, Girard Luc, Suen Wai-Sing, Chung Lap-ping, Tin Vicky P C, Lam Wah-kit, Minna John D, Wong Maria P
University Department of Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong SAR, China.
J Thorac Oncol. 2006 Nov;1(9):932-42.
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.
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 GeneChip HG-U133A.
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).
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.
支气管源性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位居首位。近几十年来，女性非吸烟者和腺癌已成为肺癌患者中一种独特的组合。从具有已知临床特征（如性别和吸烟习惯）的患者中建立的肺癌细胞系将有助于未来肺癌的研究。
从患有原发性肺腺癌且在年龄、性别、吸烟习惯、肿瘤分期和既往治疗方面具有不同临床特征的中国患者中建立了四个新的肺腺癌细胞系（HKULC 1-4）。通过免疫组织化学和生长动力学研究、裸鼠致瘤性试验、表皮生长因子受体（EGFR）基因突变分析、原位杂交以及使用Affymetrix GeneChip HG-U133A进行基因表达谱分析对它们进行了表征。
新建立的HKULC肺腺癌细胞系传代超过70次，并表现出肿瘤细胞系的形态学、免疫组织化学特征和生长动力学。四个HKULC细胞系之一，HKULC 3（源自一名患有肺腺癌的女性非吸烟患者），被发现EGFR基因外显子19有缺失。EGFR原位杂交显示这些细胞系中没有EGFR基因扩增。HKULC 1和4接种到裸鼠后形成肿瘤异种移植物。鉴定出71个差异表达或具有类别预测意义的基因列表。这些基因包括假定的肿瘤抑制基因（DKK3、SERPINF1、CDH11、DSC3和KLF6）、参与EGFR途径或与之相关的基因（ERBB3、MUC1、VAV1）、参与细胞周期和增殖调节的基因（CDKN1A和CDKN2A）、一个假定的癌基因（EEF1A2）以及一个与转移相关的基因（MTSS1）。
从具有不同临床特征的患者中建立了四个新的肺腺癌细胞系。这些具有特征的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。
