Establishment and characterization of a penile cancer cell line, penl1, with a deleterious TP53 mutation as a paradigm of HPV-negative penile carcinogenesis.
Establishment and characterization of a penile cancer cell line, penl1, with a deleterious TP53 mutation as a paradigm of HPV-negative penile carcinogenesis.
复制标题
具有有害 TP53 突变的阴茎癌细胞系 penl1 的建立和表征，作为 HPV 阴性阴茎癌发生的范例
DOI：
10.18632/oncotarget.10098
复制
发表时间：
2016-08-09
期刊：
影响因子：
--
通讯作者：
Han H
中科院分区：
文献类型：
--
作者：
Chen J;Yao K;Li Z;Deng C;Wang L;Yu X;Liang P;Xie Q;Chen P;Qin Z;Ye Y;Liu Z;Zhou F;Zhang Z;Han H
目的建立阴茎癌（PeCa）细胞系，为研究阴茎癌发生的分子机制和检测治疗药物奠定基础。材料与方法从21例新鲜肿瘤组织中成功建立了两株PeCa细胞系。从阴茎鳞状细胞癌（PeSCC）的淋巴结转移（LNM）中分离出一个名为Penl 1的细胞系，该细胞系为常见类型，并在此进行了全面表征。我们对Penl 1细胞系的深入表征分析包括形态学、致瘤性、遗传特征、蛋白质表达、生物学和化学敏感性。Penl1基因经STR分型鉴定。结果比较组织形态学、遗传学特征和蛋白质表达模式，发现该细胞系与其相应的LNM具有本质上的相似性。对Penl 1细胞系的深入表征分析揭示了免疫缺陷小鼠的致瘤性、阴性人乳头瘤病毒（HPV）和支原体感染、TP53突变以及对顺铂和表阿霉素的敏感性。STR DNA分型与三个国际细胞库中的任何细胞系均不匹配。本研究的局限性在于，一名患者不能代表PeCa的完全异质性，尤其是原发性肿瘤。结论我们建立了一个HPV阴性、中分化的PeCa细胞模型，该模型具有TP53错义突变，来自普通型PeSCC患者。初步的致癌性和化疗敏感性研究表明，该细胞模型携带抑癌基因突变，对化疗药物敏感。
Purpose To establish penile cancer (PeCa) cell lines for the study of molecular mechanisms of carcinogenesis and testing therapeutic reagents. Materials and Methods We successfully established two PeCa cell lines from fresh tumor tissues from 21 cases. One cell line named Penl1 was isolated from a lymph node metastasis (LNM) of penile squamous cell carcinoma (PeSCC), usual type and comprehensively characterized here. Our in-depth characterization analysis of the Penl1 cell line included morphology, tumorigenicity, genetic characteristics, protein expression, biology, and chemosensitivity. Penl1 was authenticated by single tandem repeat (STR) DNA typing. Results Comparative histomorphology, genetic characteristics, and protein expression patterns revealed essential similarities between the cell line and its corresponding LNM. In-depth characterization analysis of Penl1 cell line revealed tumorigenicity in immunodeficient mice, negative human papilloma virus (HPV) and mycoplasma infection, TP53 mutations and sensitivity to cisplatin and epirubicin. STR DNA typing did not match any cell lines within three international cell banks. The limitation of this study is that one patient cannot represent the complete heterogeneity of PeCa, especially primary tumor. Conclusions We established and characterized an HPV-negative and moderately differentiated PeCa cell model with a TP53 missense mutation from a PeSCC, usual type patient. A preliminarily study of carcinogenesis and chemosensitivity suggests that this cell model carries a tumor suppressor gene mutation and is sensitive to chemotherapy drugs.