Park Chaehwa, Lee Inkyoung, Kang Won Ki
Cancer Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, 135-710, Korea.
Int J Mol Med. 2006 May;17(5):715-20.
Senescence limits cellular proliferation, and therefore might be a mechanism which could suppress the progression of cancer. Herein we show that E2F1, a transcription factor essential to a cell cycle progress and a main target of tumor suppressor Rb, is a critical barrier for the induction of senescence. Human cancer cells transfected with siE2F1 were shown to express replicative senescence markers, in addition to yielding positive results upon SA-beta-Gal staining. Consistent with the notion of the critical role in senescence of E2F1, cells which overexpressed E2F1 proved to be immune to the induction of senescence. Importantly, it appears that E2F1 depletion-induced cancer cell senescence is not reliant on the integrity of either Rb or p53. Our results provide a molecular explanation for the selectivity with which senescence induction occurs, and also provides insights into the possibility of using E2F1 as a therapeutic target in the treatment of cancer.
细胞衰老会限制细胞增殖，因此可能是一种能够抑制癌症进展的机制。在此我们表明，E2F1作为细胞周期进程所必需的转录因子以及肿瘤抑制因子Rb的主要靶点，是诱导衰老的关键障碍。转染了siE2F1的人类癌细胞除了在SA-β-Gal染色中呈阳性结果外，还显示出表达复制性衰老标志物。与E2F1在衰老中起关键作用的观点一致，过表达E2F1的细胞被证明对衰老诱导具有抗性。重要的是，似乎E2F1缺失诱导的癌细胞衰老不依赖于Rb或p53的完整性。我们的结果为衰老诱导发生的选择性提供了分子解释，也为将E2F1用作癌症治疗的靶点的可能性提供了见解。
