Multiple effects of paclitaxel are modulated by a high c-myc amplification level

Maria Grazia Bottone, Cristiana Soldani, Gianluca Tognon, Chiara Gorrini, M. Claudia Lazzè, Olivier Brison, Marina Ciomei, Carlo Pellicciari, A. Ivana Scovassi

Research output: Contribution to journalArticlepeer-review

Abstract

Paclitaxel affects microtubule stability by binding to β-tubulin, thus leading to cell accumulation in the G2/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.

Original languageEnglish
Pages (from-to)49-59
Number of pages11
JournalExperimental Cell Research
Volume290
Issue number1
DOIs
Publication statusPublished - Oct 15 2003

Keywords

  • Apoptosis
  • c-myc
  • Colon carcinoma cells
  • Paclitaxel
  • Phosphorylated c-Myc

ASJC Scopus subject areas

  • Cell Biology

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