Nature：细胞衰老与肿瘤形成之间存在多层次关系

生物谷

生物谷报道：癌症普遍被认为是失控的细胞增殖，但在很多癌症的早期阶段。致癌基因的表达与细胞衰老有关。现在，研究人员已经找到了对这一现象的一个可能的解释。该研究结果发表于最新一期的《Nature》杂志上。

两个小组报告了由致癌基因诱导的衰老与DNA损伤响应之间的一个联系。被激发的致癌基因能引起异常的DNA复制，从而引起DNA损伤，后者又能导致细胞衰老。细胞衰老以前被发现在活体中是肿瘤形成的一个障碍，所以由致癌基因诱导的衰老可能是对癌症的一种先天性防御。但其效果却经常因进一步的突变而丧失。了解细胞衰老与肿瘤形成之间的多层次关系，可能有助于开发基于衰老标记的诊断和预后工具。

FIGURE 1. DNA damage accumulation and DDR activation in OIS cells.

a, SDF of the indicated DDR factors in OIS cells. Means s.d. indicate the fraction of SDF-positive cells in empty-vector (pBABE)-infected quiescent cells (Q) or senescent cells (S). Proliferating cells DDR is similar to quiescent cells. b, CHK2 pT68, CHK1 pS345, p53 pS15, p21, p16, p53 and hypophosphorylated Rb accumulate in senescent cells; an asterisk highlights the altered mobility of CHK2. Rad17 and vinculin are loading controls. c, d, DNA breaks accumulate in OIS cells as demonstrated by TUNEL (c) and comet assay under denaturing conditions (d).

原文出处：

Nature Volume 444 Number 7119

Oncogene-induced senescence is a DNA damage response triggered by DNA hyper-replication p638

Raffaella Di Micco, Marzia Fumagalli, Angelo Cicalese, Sara Piccinin, Patrizia Gasparini, Chiara Luise, Catherine Schurra, Massimiliano Garre', Paolo Giovanni Nuciforo, Aaron Bensimon, Roberta Maestro, Pier Giuseppe Pelicci and Fabrizio d'Adda di Fagagna

doi:10.1038/nature05327

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