Retinoic acid induced death of ovarian carcinoma cells correlates with c-myc stimulation

Int J Cancer. 1995 May 29;61(5):649-57. doi: 10.1002/ijc.2910610511.


In the ovarian adenocarcinoma subline N.I, all-trans retinoic acid (ATRA) induced substantial cell death. This response was elicited only at decreased serum levels. Exposure of N.I cells to increasing concentrations of ATRA was accompanied by a considerable up-regulation of c-myc transcript levels that correlated with the rate of cell killing, which itself was an active process as judged by sustained transcriptional expression. ATRA-triggered rounding and detaching of single cells from the substratum was accompanied by degradation of genomic DNA. We show that the N.I model cell line, which is otherwise highly ATRA-resistant, can undergo an ATRA-triggered suicide program when serum is limited. The accompanying c-myc up-regulation seems to be mediated by retinoic-acid-receptor-independent pathways involving membrane-associated phospholipases instead, because manoalide partly suppressed c-myc induction by ATRA but left constitutive c-myc expression unaffected.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / pathology*
  • Apoptosis*
  • Blotting, Northern
  • Female
  • Gene Expression
  • Genes, myc / genetics*
  • Humans
  • Microscopy, Phase-Contrast
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / pathology*
  • Tretinoin / pharmacology*
  • Tumor Cells, Cultured


  • Tretinoin