Nuclear factor-κB, induced in human carcinoma cell line A2780 by the new anthracycline men 10755, is devoid of transcriptional activity
✍ Scribed by Grazia Camarda; Monica Binaschi; Carlo A. Maggi; Cristina Goso
- Publisher
- John Wiley and Sons
- Year
- 2002
- Tongue
- French
- Weight
- 552 KB
- Volume
- 102
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
Abstract
The new disaccharide anthracycline MEN 10755 induces activation of both NF‐κB and p53 transcription factors in A2780 cells. Nevertheless, pharmacologic inhibition of NF‐κB activation does not modify the sensitivity of A2780 cells to MEN 10755 treatment. To better characterize the role of NF‐κB in MEN 10755–induced cytotoxicity, we analyzed the expression of a number of genes that are known to be regulated by NF‐κB. None of these genes is modified by MEN 10755 treatment. On the contrary, our results suggest that the p53 DNA damage‐responsive pathway is fully activated in A2780 cells, several genes controlled by p53 being up‐ or downregulated according to the described action of p53 on their promoters. Thus, in the A2780 cell line, the role of p53 in transducing the DNA‐damage signal appears to be relevant, whereas NF‐κB, although activated, appears to be nonfunctional. Other human carcinoma cell lines besides A2780 activate NF‐κB DNA binding in response to MEN 10755 treatment, but again, this binding does not always lead to target gene activation. These results suggest that other factors, tumor type‐specific and different from mere activation, could influence NF‐κB transcriptional activity. Therefore, care should be taken when considering the pharmacologic inhibition of NF‐κB as a means to improve anticancer therapy efficacy. © 2002 Wiley‐Liss, Inc.