Garner-Hamrick P A, Fisher C
Cell and Molecular Biology, Pharmacia and Upjohn, Inc., Kalamazoo, MI 49001, USA.
Int J Cancer. 1998 May 29;76(5):720-8. doi: 10.1002/(sici)1097-0215(19980529)76:5<720::aid-ijc18>3.0.co;2-7.
Cell cycle progression in mammalian cells is regulated by a family of cyclin-dependent kinases (cdks) that are activated by a family of 3 cdc25 phosphatases: cdc25A, cdc25B and cdc25C. We examined the expression of mRNA and protein of all 3 cdc25s during the HeLa cell cycle, and found that cdc25B protein has a unique and limited pattern of expression relative to other cdc25 homologs. Antisense oligonucleotides reduced cdc25B mRNA levels and dysregulated protein expression, while inhibiting S-phase progression in synchronized HeLa cells. Scrambled control oligonucleotides had no effect. Antisense oligonucleotides transfected in early G2-phase had no effect on cell cycle progression. A direct correlation between down-regulation of cdc25B and inhibition of thymidine incorporation was found using several oligonucleotides. Our results suggest a role for cdc25B in S-phase and demonstrate that inhibition of cdc25B has persistent antiproliferative effects.
哺乳动物细胞中的细胞周期进程由一类细胞周期蛋白依赖性激酶（cdks）调控，这类激酶由3种cdc25磷酸酶激活，即cdc25A、cdc25B和cdc25C。我们检测了HeLa细胞周期中所有3种cdc25的mRNA和蛋白质表达，发现相对于其他cdc25同源物，cdc25B蛋白具有独特且有限的表达模式。反义寡核苷酸降低了cdc25B的mRNA水平并使蛋白质表达失调，同时抑制了同步化HeLa细胞的S期进程。随机对照寡核苷酸则无此作用。在G2期早期转染的反义寡核苷酸对细胞周期进程没有影响。使用几种寡核苷酸发现cdc25B的下调与胸苷掺入抑制之间存在直接相关性。我们的结果表明cdc25B在S期发挥作用，并证明抑制cdc25B具有持续的抗增殖作用。
