Gorrini Chiara, Donzelli Maddalena, Torriglia Alicia, Supino Rosanna, Brison Olivier, Bernardi Rosa, Negri Claudia, Denegri Marco, Counis Marie-France, Ranzani G Nadia, Scovassi A Ivana
Istituto di Genetica Molecolare CNR, I-27100 Pavia, Italy.
Int J Mol Med. 2003 Jun;11(6):737-42.
We have recently demonstrated that a high c-myc endogenous amplification level confers an apoptosis-prone phenotype to serum-deprived colon carcinoma SW613-S cells. The aim of this study was to gain new insights into the features of c-myc-dependent apoptosis, by extending our analysis to different apoptogenic stimuli. The study was carried out on clones, derived from the human colon carcinoma SW613-S cell line, which harbor different levels of endogenous c-myc amplification, and on isogenic cell lines with an enforced c-myc overexpression. Our results indicate that cells with endogenous or transfected exogenous c-myc overexpression (SW613-12A1 and -2G1mycP2Tu1 cell lines, respectively), activate the apoptotic machinery in response to the treatment with etoposide, doxorubicin and vitamin D3, which induce apoptosis through the death receptor Fas. The low levels of c-myc expression present in SW613-B3 and -B3mycC5, seem to be unable to activate Fas-mediated apoptosis, thus suggesting that only a high c-myc expression can bypass the lack of Fas receptor. Apoptosis induction mediated by DNA damage and long-term culture was independent of c-myc expression. A pathway of apoptosis characterized by the activation of the enzyme L-DNase II, was observed in both 12A1 and B3 cell lines.
我们最近证明，高内源性c-myc扩增水平赋予血清剥夺的结肠癌SW613-S细胞易于凋亡的表型。本研究的目的是通过将分析扩展到不同的凋亡诱导刺激，来深入了解c-myc依赖性凋亡的特征。该研究在源自人结肠癌SW613-S细胞系的克隆上进行，这些克隆具有不同水平的内源性c-myc扩增，以及在强制过表达c-myc的同基因细胞系上进行。我们的结果表明，内源性或转染外源性c-myc过表达的细胞（分别为SW613-12A1和-2G1mycP2Tu1细胞系），在接受依托泊苷、阿霉素和维生素D3处理时激活凋亡机制，这些物质通过死亡受体Fas诱导凋亡。SW613-B3和-B3mycC5中存在的低水平c-myc表达似乎无法激活Fas介导的凋亡，因此表明只有高c-myc表达才能绕过Fas受体的缺失。由DNA损伤和长期培养介导的凋亡诱导与c-myc表达无关。在12A1和B3细胞系中均观察到以L-DNase II酶激活为特征的凋亡途径。
