Wistuba I I, Behrens C, Milchgrub S, Syed S, Ahmadian M, Virmani A K, Kurvari V, Cunningham T H, Ashfaq R, Minna J D, Gazdar A F
Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas 75235-8593, USA.
Clin Cancer Res. 1998 Dec;4(12):2931-8.
Although human tumor-derived cell lines play an important role in the investigation of cancer biology and genetics, there is no comprehensive study comparing tumor cell line properties with those of the individual tumors from which they were derived. We compared the properties of a series of 18 human breast cancer cell lines that were cultured for a median period of 25 months (range, 9-60 months) and their corresponding archival tumor tissues. We compared morphological characteristics, ploidy, and immunohistochemical expression of estrogen receptors, progesterone receptors, and HER2/neu and p53 proteins. For 17 of these cases, we also tested for allelic losses at 18 chromosomal regions frequently deleted in breast tumors using 51 polymorphic microsatellite markers, and we determined the TP53 gene mutation status in exons 5 to 10. There was an excellent correlation between the breast tumor cell lines and their corresponding tumor tissues for morphological features (100%); presence of aneuploidy (87%); immunohistochemical expression of estrogen receptors (87%), progesterone receptors (73%), and HER2/neu (93%) and p53 proteins (100%); allelic loss at all of the chromosomal regions analyzed (82-100% concordance); and TP53 gene mutations (75%). The same parental allele was lost in 279 (99%) of 281 of the comparisons of allelic losses. The fractional allelic loss indices (a reflection of the total allelic loss) of the cell lines and their corresponding tumor tissues were identical or similar in 15 (88%) of 17 paired comparisons. Although our previous studies (A. Gazdar et al., Int. J. Cancer, in press) indicated that only a subset of primary breast carcinomas that have several features indicative of advanced tumors with poor prognosis can be successfully cultured, the cell lines retain the properties of their parental tumors for lengthy culture periods and, thus, provide suitable model systems for biomedical studies.
尽管人肿瘤来源的细胞系在癌症生物学和遗传学研究中发挥着重要作用，但尚无全面研究将肿瘤细胞系的特性与其来源的个体肿瘤的特性进行比较。我们比较了一系列18个人类乳腺癌细胞系（培养中位时间为25个月，范围9 - 60个月）及其相应的存档肿瘤组织的特性。我们比较了形态学特征、倍性以及雌激素受体、孕激素受体、HER2/neu和p53蛋白的免疫组化表达。对于其中17例，我们还使用51个多态性微卫星标记检测了在乳腺肿瘤中经常缺失的18个染色体区域的等位基因缺失情况，并确定了外显子5至10中的TP53基因突变状态。乳腺肿瘤细胞系与其相应肿瘤组织在形态学特征（100%）、非整倍体的存在（87%）、雌激素受体（87%）、孕激素受体（73%）、HER2/neu（93%）和p53蛋白（100%）的免疫组化表达、所有分析染色体区域的等位基因缺失（一致性为82 - 100%）以及TP53基因突变（75%）方面存在极好的相关性。在281次等位基因缺失比较中的279次（99%）中，丢失的是相同的亲本等位基因。在17对配对比较中的15对（88%）中，细胞系及其相应肿瘤组织的部分等位基因缺失指数（反映总等位基因缺失情况）相同或相似。尽管我们之前的研究（A. Gazdar等人，《国际癌症杂志》，即将发表）表明，只有一部分具有多种提示预后不良的晚期肿瘤特征的原发性乳腺癌能够成功培养，但这些细胞系在长时间培养过程中保留了其亲本肿瘤的特性，因此为生物医学研究提供了合适的模型系统。
