Tetsu Osamu, McCormick Frank
Cancer Research Institute and Comprehensive Cancer Center, University of California, San Francisco, CA 94143, USA.
Cancer Cell. 2003 Mar;3(3):233-45. doi: 10.1016/s1535-6108(03)00053-9.
We have investigated the contribution of CDK4 and CDK2 inhibition to G1 arrest in colon cancers following inhibition of the MEK/MAP kinase pathway. CDK4 inhibition is sufficient to cause arrest, but inhibition of CDK2 by p27 Kip1 redistribution or ectopic expression has no effect on proliferation. Likewise, inhibition of CDK2 through expression of dominant-negative (DN) CDK2 or antisense oligonucleotides did not prevent cell proliferation in these cells. We therefore tested whether CDK2 activity is dispensable in other cells. Surprisingly, osteosarcomas and Rb-negative cervical cancers continued to proliferate after depletion of CDK2 through antisense oligonucleotides or small interfering (si) RNA. Here we report of sustained cell proliferation in the absence of CDK2, and we suggest that CDK2 is not a suitable target for cancer therapy.
我们研究了在抑制MEK/MAP激酶途径后，CDK4和CDK2抑制对结肠癌G1期阻滞的作用。抑制CDK4足以导致细胞阻滞，但通过p27 Kip1重新分布或异位表达抑制CDK2对增殖没有影响。同样，通过表达显性负性（DN）CDK2或反义寡核苷酸抑制CDK2也不能阻止这些细胞的增殖。因此，我们测试了CDK2活性在其他细胞中是否是可有可无的。令人惊讶的是，骨肉瘤和Rb阴性宫颈癌在通过反义寡核苷酸或小干扰（si）RNA耗尽CDK2后仍继续增殖。在此我们报告了在没有CDK2的情况下细胞持续增殖的情况，并提出CDK2不是癌症治疗的合适靶点。
