We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Effects on normal fibroblasts and neuroblastoma cells of the activation of the p53 response by the nuclear export inhibitor leptomycin B.
- Authors
Smart, Philip; Lane, E Birgitte; Lane, David P; Midgley, Carol; Vojtesek, Borek; Laín, Sonia
- Abstract
p53 tumour suppressor protein levels and p53-dependent transcriptional activity have been recently shown to increase in cells treated with leptomycin B (LMB), an inhibitor of nuclear export. Experiments presented here show that LMB treatment leads to growth arrest and a senescence-like phenotype in human normal fibroblast cultures. This effect is reversible after removal of the drug and further passage by trypsinization. Instead, LMB has a strong cytotoxic effect on human neuroblastoma cell lines even at nanomolar concentrations. In both these cell types the effects of LMB are attenuated when the activity of the endogenous wild type p53 protein is abrogated by overexpression of a dominant negative p53 mutant. We conclude that the induction of the p53 response by LMB plays an important role in the effects of this drug on cultured cells.
- Subjects
P53 antioncogene; TUMOR suppressor genes; NEUROBLASTOMA; FIBROBLASTS
- Publication
Oncogene, 1999, Vol 18, Issue 51, p7378
- ISSN
0950-9232
- Publication type
Article
- DOI
10.1038/sj.onc.1203260