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两种新型人肺鳞状细胞癌和腺癌细胞系的分子与生物学特征

Molecular and biological features of two new human squamous and adenocarcinoma of the lung cell lines.

作者信息

Gasperi-Campani A, Roncuzzi L, Ricotti L, Lenzi L, Gruppioni R, Sensi A, Zini N, Zoli W, Amadori D

机构信息

Department of Experimental Pathology, University of Bologna, Italy.

出版信息

Cancer Genet Cytogenet. 1998 Nov;107(1):11-20. doi: 10.1016/s0165-4608(98)00076-4.

Abstract

Two human cancer cell lines were established from metastatic lesions of an adenocarcinoma (RAL) and a squamous cell (CAEP) carcinoma of the lung. The clinical histories of the patients from whom the cell lines were derived are reported. The lines were maintained in continuous culture with doubling times of 65 (RAL) and 50 (CAEP) hours. The RAL and CAEP cell lines, whose morphology and ultrastructural features are presented, showed extensively rearranged karyotypes with modal number of 85 (RAL) and 98 (CAEP). In particular, chromosome 2 pentasomy and several clonal markers were evident in the RAL cells, whereas a telomeric deletion of chromosome 1, del (1)(q32), was observed in the CAEP cells. The morphologic data were confirmed by high expression of specific antigens for each histotype. A marked positivity of the neuron-specific enolase (NSE) levels was evident by immunoenzymatic assays in the cell lines cytosol with respect to those present in the respective patient's sera. No amplification or rearrangements were evident in the CMYC, LMYC, NMYC, INT-2, ERBB2, HRAS, KRAS, MOS, HST-1 genes by Southern blotting analysis in each cell line. Point mutations in exon 1 of KRAS and in exon 7 of TP53 were evident by polymerase chain reaction (PCR)-DNA sequencing in the RAL cell line, whereas no alterations were present in the HRAS and RB genes. The four genes studied did not show point mutations in the CAEP cell line. The RAL cell line was resistant to all the drugs tested, whereas the CAEP cells were sensitive to vinblastine. These cell lines may represent useful experimental models to investigate lung cancer biology and anticancer drug response.

摘要

从肺腺癌(RAL)和肺鳞状细胞癌(CAEP)的转移病灶中建立了两个人类癌细胞系。报告了这些细胞系所源自患者的临床病史。这些细胞系在连续培养中维持,倍增时间分别为65小时(RAL)和50小时(CAEP)。文中呈现了RAL和CAEP细胞系的形态和超微结构特征,其核型广泛重排,众数分别为85(RAL)和98(CAEP)。特别是,RAL细胞中明显存在2号染色体五体性和几个克隆标记,而在CAEP细胞中观察到1号染色体的端粒缺失,即del(1)(q32)。通过每种组织类型特异性抗原的高表达证实了形态学数据。免疫酶测定显示,细胞系胞质溶胶中神经元特异性烯醇化酶(NSE)水平相对于各自患者血清中的水平呈明显阳性。通过Southern印迹分析,每个细胞系中的CMYC、LMYC、NMYC、INT-2、ERBB2、HRAS、KRAS、MOS、HST-1基因均未出现扩增或重排。通过聚合酶链反应(PCR)-DNA测序,RAL细胞系中KRAS外显子1和TP53外显子7存在点突变,而HRAS和RB基因未发生改变。所研究的四个基因在CAEP细胞系中未显示点突变。RAL细胞系对所有测试药物均耐药,而CAEP细胞对长春碱敏感。这些细胞系可能是研究肺癌生物学和抗癌药物反应的有用实验模型。

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