Deletion of the p16INK4A gene in ex vivo acute adult T cell lymphoma/leukemia cells and methylation of the p16INK4A promoter in HTLV type I-infected T cell lines.
Deletion of the p16INK4A gene in ex vivo acute adult T cell lymphoma/leukemia cells and methylation of the p16INK4A promoter in HTLV type I-infected T cell lines.
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DOI：
10.1089/088922200308701
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发表时间：
2000-05
影响因子：
1.5
通讯作者：
R. Trovato;A. Cereseto;S. Takemoto;A. Gessain;T. Watanabe;T. Waldmann;G. Franchini
中科院分区：
文献类型：
--
作者：
R. Trovato;A. Cereseto;S. Takemoto;A. Gessain;T. Watanabe;T. Waldmann;G. Franchini
p16 INK 4A和p15 INK 4 B蛋白与细胞周期蛋白D-CDK 4/6复合物结合的化学计量调节细胞进入细胞周期的G1期。因此，它们的表达水平在维持受调节的细胞生长中是必不可少的。在几种肿瘤中，已经报道了这些基因的缺失，最近，启动子甲基化被认为是降低这些细胞周期抑制剂蛋白表达的替代机制。在这里，我们研究了甲基化状态和完整性的p16 INK 4A和p15 INK 4 B基因在8个慢性HTLV-I感染的T细胞系和体外细胞从14 ATLL患者。携带这两种基因的位点的缺失在HTLV-I感染的T细胞系中未发现，但在8例急性ATLL病例中的7例中发现，而在慢性病例或淋巴瘤类型的受影响淋巴结的PBMC中均未发现。相反，一个或两个基因的部分或完全甲基化仅在慢性HTLV-I T细胞中发现。因此，HTLV-I感染靶向p16 INK 4A和p15 INK 4 B基因座在体外和体内，虽然机制可能不同。
The stoichiometry of the p16INK4A and p15INK4B proteins bound to the cyclin D-CDK4/6 complex regulates the entry of cells into the G1 phase of the cell cycle. Thus, their level of expression is essential in maintaining regulated cell growth. In several tumors, deletion of these genes has been reported and, more recently, promoter methylation has been suggested as an alternative mechanism to decrease the expression of these cell cycle inhibitor proteins. Here, we studied the methylation status and the integrity of the p16INK4A and p15INK4B genes in 8 chronically HTLV-I-infected T cell lines and in ex vivo cells from 14 ATLL patients. Deletion of the locus carrying both genes was not found in the HTLV-I-infected T cell lines but was found in seven of eight acute ATLL cases and in none of the PBMCs from the chronic cases or the affected lymph nodes of the lymphoma type. In contrast, partial or complete methylation of one or both genes was found only in chronically HTLV-I T cells. Thus, HTLV-I infection targets the p16INK4A and p15INK4B loci both in vitro and in vivo, although the mechanisms may differ.