Retinoic acid induced death of ovarian carcinoma cells correlates with c-myc stimulation.
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.
Krupitza
G
G
Department of Internal Medicine I, University of Vienna, Austria.
Hulla
W
W
Harant
H
H
Dittrich
E
E
Kallay
E
E
Huber
H
H
Grunt
T
T
Dittrich
C
C
D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology*; D017209:Apoptosis; D015152:Blotting, Northern; D005260:Female; D015870:Gene Expression; D016259:Genes, myc / Q000235:genetics*; D006801:Humans; D008858:Microscopy, Phase-Contrast; D010051:Ovarian Neoplasms / Q000235:genetics / Q000473:pathology*; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D014212:Tretinoin