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通过爱泼斯坦-巴尔病毒转化建立致瘤性人B淋巴母细胞系的体外培养

In vitro establishment of tumorigenic human B-lymphoblastoid cell lines transformed by Epstein-Barr virus.

作者信息

Takahashi Tomoko, Kawabe Tamae, Okazaki Yuichi, Itoh Chie, Noda Keisuke, Tajima Manami, Satoh Misako, Goto Makoto, Mitsui Youji, Tahara Hidetoshi, Ide Toshinori, Furuichi Yasuhiro, Sugimoto Masanobu

机构信息

Center for Tsukuba Advanced Research Alliance, University of Tsukuba 1, Tennoudai, Tsukuba, Ibaraki, Japan.

出版信息

DNA Cell Biol. 2003 Nov;22(11):727-35. doi: 10.1089/104454903770946700.

Abstract

We studied tumorigenic and phenotypic characteristics of pre- and postimmortal human B-lymphoblastoid cell lines (LCLs) transformed by Epstein-Barr virus (EBV): preimmortal LCLs showed low telomerase activity and a normal diploid karyotype while postimmortal LCLs showed much higher telomerase activity and maintained a clonal aneuploidic state. Among five postimmortal LCLs tested, LCLs N0005 and N6803 formed colonies in agar medium and showed marked aneuploidy, and N6803 was transplantable into nude mice indicating that it had a complete malignant phenotype, but all preimmortal LCLs and the remaining three postimmortal LCLs lacked these characteristics. The products of tumor suppresser genes, p16(INK4A) and pRb, were downregulated in these two LCLs, and the p53 gene was mutated in N0005 LCL. We believe these results showed for the first time that some postimmortal EBV-transformed LCLs can become tumorigenic, contrary to previous reports, and that these LCLs provide an in vitro model of tumorigenesis induced by EBV.

摘要

我们研究了由爱泼斯坦-巴尔病毒(EBV)转化的永生前后人类B淋巴细胞系(LCLs)的致瘤性和表型特征:永生前的LCLs显示出低端粒酶活性和正常的二倍体核型,而永生后的LCLs显示出更高的端粒酶活性并维持克隆性非整倍体状态。在测试的五个永生后的LCLs中,LCLs N0005和N6803在琼脂培养基中形成菌落并显示出明显的非整倍体,并且N6803可移植到裸鼠中,表明它具有完整的恶性表型,但所有永生前的LCLs和其余三个永生后的LCLs缺乏这些特征。肿瘤抑制基因p16(INK4A)和pRb的产物在这两个LCLs中下调,并且p53基因在N0005 LCL中发生突变。我们相信这些结果首次表明,与先前的报道相反,一些永生后的EBV转化的LCLs可以变得具有致瘤性,并且这些LCLs提供了一个EBV诱导的肿瘤发生的体外模型。

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