Gosselin Karo, Martien Sébastien, Pourtier Albin, Vercamer Chantal, Ostoich Peter, Morat Luc, Sabatier Laure, Duprez Laurence, T'kint de Roodenbeke Claire, Gilson Eric, Malaquin Nicolas, Wernert Nicolas, Slijepcevic Predrag, Ashtari Marjan, Chelli Fazia, Deruy Emeric, Vandenbunder Bernard, De Launoit Yvan, Abbadie Corinne
Université Lille Nord de France, CNRS, UMR8161, UDSL, Institut Pasteur de Lille, Lille, France.
Cancer Res. 2009 Oct 15;69(20):7917-25. doi: 10.1158/0008-5472.CAN-08-2510. Epub 2009 Oct 13.
Studies on human fibroblasts have led to viewing senescence as a barrier against tumorigenesis. Using keratinocytes, we show here that partially transformed and tumorigenic cells systematically and spontaneously emerge from senescent cultures. We show that these emerging cells are generated from senescent cells, which are still competent for replication, by an unusual budding-mitosis mechanism. We further present data implicating reactive oxygen species that accumulate during senescence as a potential mutagenic motor of this post-senescence emergence. We conclude that senescence and its associated oxidative stress could be a tumor-promoting state for epithelial cells, potentially explaining why the incidence of carcinogenesis dramatically increases with advanced age.
对人类成纤维细胞的研究使人们将衰老视为一种抗肿瘤发生的屏障。利用角质形成细胞，我们在此表明，部分转化的致瘤细胞会从衰老培养物中系统性地自发出现。我们证明，这些新出现的细胞是由仍具有复制能力的衰老细胞通过一种不寻常的出芽 - 有丝分裂机制产生的。我们进一步提供的数据表明，衰老过程中积累的活性氧是这种衰老后细胞出现的潜在诱变动力。我们得出结论，衰老及其相关的氧化应激可能是上皮细胞的一种促癌状态，这可能解释了为什么癌症发生率会随着年龄增长而急剧上升。
