Bottone Maria Grazia, Soldani Cristiana, Tognon Gianluca, Gorrini Chiara, Lazzè M Claudia, Brison Olivier, Ciomei Marina, Pellicciari Carlo, Scovassi A Ivana
Dipartimento di Biologia Animale, Università di Pavia, Italy.
Exp Cell Res. 2003 Oct 15;290(1):49-59. doi: 10.1016/s0014-4827(03)00312-4.
Paclitaxel affects microtubule stability by binding to beta-tubulin, thus leading to cell accumulation in the G(2)/M phase, polyploidization, and apoptosis. Because both cell proliferation and apoptosis could be somehow regulated by the protooncogene c-myc, in this work we have investigated whether the c-myc amplification level could modulate the multiple effects of paclitaxel. To this aim, paclitaxel was administered to SW613-12A1 and -B3 human colon carcinoma cell lines (which are characterized by a high and low c-myc endogenous amplification level, respectively), and to the B3mycC5 cell line, with an enforced exogenous expression of c-myc copies. In this experimental system, we previously demonstrated that a high endogenous/exogenous level of amplification of c-myc enhances serum deprivation- and DNA damage-induced apoptosis. Accordingly, the present results indicate that a high c-myc amplification level potentiates paclitaxel cytotoxicity, confers a multinucleated phenotype, and promotes apoptosis to a great extent, thus suggesting that c-myc expression level is relevant in modulating the cellular responses to paclitaxel. We have recently shown in HeLa cells that the phosphorylated form of c-Myc accumulates in the nucleus, as distinct nucleolar and extranucleolar spots; here, we demonstrated that, after the treatment with paclitaxel, phosphorylated c-Myc undergoes redistribution, becoming diffused in the nucleoplasm.
紫杉醇通过与β-微管蛋白结合来影响微管稳定性，从而导致细胞在G(2)/M期积累、多倍体化和凋亡。由于细胞增殖和凋亡在某种程度上都可能受原癌基因c-myc调控，因此在本研究中，我们探究了c-myc的扩增水平是否能够调节紫杉醇的多种效应。为此，我们将紫杉醇分别作用于SW613 - 12A1和 - B3人结肠癌细胞系（其特征分别为c-myc内源性扩增水平高和低）以及具有增强的c-myc拷贝外源性表达的B3mycC5细胞系。在这个实验系统中，我们之前证明了c-myc的高内源性/外源性扩增水平会增强血清剥夺和DNA损伤诱导的凋亡。相应地，目前的结果表明，高c-myc扩增水平会增强紫杉醇的细胞毒性，赋予多核表型，并在很大程度上促进凋亡，从而表明c-myc的表达水平在调节细胞对紫杉醇的反应中具有相关性。我们最近在HeLa细胞中发现，磷酸化形式的c-Myc会在细胞核中积累，形成不同的核仁及核仁外斑点；在此，我们证明，在用紫杉醇处理后，磷酸化的c-Myc会发生重新分布，扩散到核质中。
