Holcomb Valerie B, Rodier Francis, Choi YongJun, Busuttil Rita A, Vogel Hannes, Vijg Jan, Campisi Judith, Hasty Paul
Department of Molecular Medicine, Institute of Biotechnology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas 78245-3207, USA.
Cancer Res. 2008 Nov 15;68(22):9497-502. doi: 10.1158/0008-5472.CAN-08-2085.
Ku80 facilitates DNA repair and therefore should suppress cancer. However, ku80(-/-) mice exhibit reduced cancer, although they age prematurely and have a shortened life span. We tested the hypothesis that Ku80 deletion suppresses cancer by enhancing cellular tumor-suppressive responses to inefficiently repaired DNA damage. In support of this hypothesis, Ku80 deletion ameliorated tumor burden in APC(MIN) mice and increased a p53-mediated DNA damage response, DNA lesions, and chromosomal rearrangements. Thus, contrary to its assumed role as a caretaker tumor suppressor, Ku80 facilitates tumor growth most likely by dampening baseline cellular DNA damage responses.
Ku80促进DNA修复，因此应该抑制癌症。然而，Ku80基因敲除的小鼠患癌几率降低，尽管它们过早衰老且寿命缩短。我们检验了这样一个假设，即Ku80基因缺失通过增强细胞对未有效修复的DNA损伤的肿瘤抑制反应来抑制癌症。支持这一假设的是，Ku80基因缺失减轻了APC（MIN）小鼠的肿瘤负担，并增强了p53介导的DNA损伤反应、DNA损伤及染色体重排。因此，与它作为一种维护性肿瘤抑制因子的假定作用相反，Ku80很可能是通过减弱细胞的基线DNA损伤反应来促进肿瘤生长的。
