Ikeda Masato, Okamoto Isamu, Tamura Kenji, Satoh Taroh, Yonesaka Kimio, Fukuoka Masahiro, Nakagawa Kazuhiko
Department of Medical Oncology, Kinki University School of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka, Japan.
Cancer Lett. 2007 Apr 18;248(2):292-8. doi: 10.1016/j.canlet.2006.08.005. Epub 2006 Sep 7.
Deregulation of survivin expression is implicated in tumorigenesis. To examine the regulation of survivin expression in response to DNA damage, we exposed A549 human lung cancer cells to ultraviolet C (UVC) radiation, which induces DNA single-strand breakage. UVC irradiation induced G(2)-M arrest that was accompanied by accumulation of p53 and subsequent down-regulation of survivin. Depletion of p53 by RNA interference prevented the UVC-induced down-regulation of survivin. Furthermore, depletion of survivin resulted in G(2)-M arrest, suggesting that down-regulation of survivin by p53 contributes to the p53-dependent G(2)-M checkpoint triggered by DNA damage.
生存素表达失调与肿瘤发生有关。为了研究DNA损伤时生存素表达的调控情况,我们将A549人肺癌细胞暴露于紫外线C(UVC)辐射下,这种辐射可诱导DNA单链断裂。UVC照射诱导了G2 - M期阻滞,同时伴有p53的积累以及随后生存素的下调。通过RNA干扰使p53缺失可阻止UVC诱导的生存素下调。此外,生存素缺失导致G2 - M期阻滞,这表明p53介导的生存素下调有助于DNA损伤触发的p53依赖的G2 - M检查点。