Lim Daina, Jocelyn Koh Mei-Xin, Yip George Wai-Cheong, Bay Boon-Huat
Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, 4 Medical Drive, Blk MD 10, S 117 597 Singapore, Singapore.
Cancer Lett. 2009 Apr 8;276(1):109-17. doi: 10.1016/j.canlet.2008.10.038. Epub 2008 Dec 4.
Metallothioneins (MTs) are a group of metal-binding proteins involved in cell proliferation, differentiation and apoptosis. The MT-2A isoform is generally the most abundant isoform among the 10 known functional MT genes. In the present study, we observed that down-regulation of the MT-2A gene in MCF-7 cells via siRNA-mediated silencing inhibited cell growth by inducing cell cycle arrest in G1-phase (G1-arrest) and a marginal increase in cells in sub-G1-phase. Scanning electron microscopic examination of the cells with silenced expression of MT-2A (siMT-2A cells) revealed essentially normal cell morphology with presence of scattered apoptotic cells. To elucidate the underlying molecular mechanism, we examined the expression of cell cycle related genes in MT-2A-silenced cells and found a higher expression of the ataxia telangiectasia mutated (ATM) gene concomitant with a lower expression of the cdc25A gene. These data suggest that MT-2A could plausibly modulate cell cycle progression from G1- to S-phase via the ATM/Chk2/cdc25A pathway.
金属硫蛋白（MTs）是一类参与细胞增殖、分化和凋亡的金属结合蛋白。MT - 2A亚型通常是已知的10种功能性MT基因中含量最丰富的亚型。在本研究中，我们观察到通过小干扰RNA（siRNA）介导的沉默作用使MCF - 7细胞中的MT - 2A基因下调，可诱导细胞周期阻滞于G1期（G1期阻滞）并使亚G1期细胞略有增加，从而抑制细胞生长。对MT - 2A表达沉默的细胞（siMT - 2A细胞）进行扫描电子显微镜检查，发现细胞形态基本正常，但存在散在的凋亡细胞。为阐明潜在的分子机制，我们检测了MT - 2A沉默细胞中细胞周期相关基因的表达，发现共济失调毛细血管扩张症突变（ATM）基因表达上调，同时细胞周期蛋白依赖性激酶25A（cdc25A）基因表达下调。这些数据表明，MT - 2A可能通过ATM/Chk2/cdc25A途径合理地调节细胞周期从G1期到S期的进程。
