Akagi T, Ono H, Shimotohno K
Virology Division, National Cancer Center Research Institute, Tokyo, Japan.
Oncogene. 1996 Apr 18;12(8):1645-52.
To understand how the growth of T-cells transformed by Human T-cell leukemia virus type I (HTLV-I) is deregulated, we analysed the expression of cell-cycle regulatory genes in HTLV-I infected and non-infected T-cell lines. We investigated the gene for 6 cyclins, 4 cyclin-dependent kinases, and 5 cyclin-dependent kinase inhibitors, and found the following: (1) HTLV-I infected T-cell lines preferentially expressed cyclin D2, whereas cyclin D3 was the major D-type cyclin in HTLV-I negative T-cell lines; (2) HTLV-I infected T-cell lines expressed strikingly low levels of p18Ink4 compared with those that were HTLV-I negative; (3) HTLV-I infected T-cell lines expressed high levels of p21Waf1/Cip1/Sdi1, whereas p21Waf1/Cip1/Sdi1 was undetectable in HTLV-I negative T-cell lines. These features were also found in T-cells immortalized by Tax1, which we established. Therefore, it is strongly suggested that Tax1 alters the expression of these cell-cycle regulatory genes.
为了解I型人类T细胞白血病病毒（HTLV-I）转化的T细胞的生长是如何失调的，我们分析了HTLV-I感染和未感染的T细胞系中细胞周期调控基因的表达。我们研究了6种细胞周期蛋白、4种细胞周期蛋白依赖性激酶和5种细胞周期蛋白依赖性激酶抑制剂的基因，结果如下：（1）HTLV-I感染的T细胞系优先表达细胞周期蛋白D2，而细胞周期蛋白D3是HTLV-I阴性T细胞系中的主要D型细胞周期蛋白；（2）与HTLV-I阴性的T细胞系相比，HTLV-I感染的T细胞系中p18Ink4的表达水平极低；（3）HTLV-I感染的T细胞系中p21Waf1/Cip1/Sdi1表达水平较高，而在HTLV-I阴性T细胞系中未检测到p21Waf1/Cip1/Sdi1。在我们建立的由Tax1永生化的T细胞中也发现了这些特征。因此，强烈提示Tax1改变了这些细胞周期调控基因的表达。
