Role of c-myc protein in hormone refractory prostate carcinoma: Cellular response to paclitaxel

Giuliana Cassinelli, Rosanna Supino, Valentina Zuco, Cinzia Lanzi, A. Ivana Scovassi, Sean C. Semple, Franco Zunino

Research output: Contribution to journalArticle

Abstract

Amplification of the c-MYC proto-oncogene is a frequent alteration in hormone refractory prostate carcinomas (HRPC). In an attempt to investigate the role of c-myc in the cellular response to paclitaxel (PTX), we used two HRPC cell lines, DU145 and PC3, characterised by different levels of the protein and by different behaviour in response to taxane. In both cell lines, PTX-induced cell death was a caspase-mediated apoptosis. In DU145 cells, PTX induced an early apoptotic response associated with upregulation of c-myc restricted to the G2/M cell population. This event appeared delayed in the presence of c-myc antisense (AS-c-myc), suggesting an upstream regulation of the protein expression. In addition, the antisense approach provided evidence of an involvement of c-myc in the apoptotic response to the taxane. In contrast, in PC3 cells, the overexpressed c-myc was not modulated by drug-treatment and the addition of AS-c-myc did not affect the cell growth inhibition of PTX. In both cell lines, PTX-induced c-myc phosphorylation was concomitant with the mitotic arrest and not related to the modulation of the activation state of AKT and MAPK kinases. Our data indicate that the cellular response to PTX of HRPC cells can involve c-myc and suggest that its pro-apoptotic role is affected by the genetic background, thus supporting a complex and differentiated HRPC cell response to taxanes.

Original languageEnglish
Pages (from-to)923-931
Number of pages9
JournalBiochemical Pharmacology
Volume68
Issue number5
DOIs
Publication statusPublished - Sep 1 2004

Keywords

  • AS-c-myc
  • c-myc
  • c-myc antisense
  • hormone refractory prostate carcinoma
  • HRPC
  • ODN
  • oligodeoxynucleotide
  • paclitaxel
  • Paclitaxel
  • PI
  • propidium iodide
  • Prostatic neoplasms
  • PTX
  • Scr-ODN
  • scrambled oligodeoxynucleotide
  • TdT-mediated dUTP nick-end labelling
  • TUNEL

ASJC Scopus subject areas

  • Pharmacology

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