title: The biological response of MCF7 breast cancer cells to proteosome inhibition or gamma-radiation is unrelated to the level of p53 induction.
abstract: The p53 tumour suppressor is stabilised following exposure to genotoxic agents, such as gamma-radiation. Cell responses to p53 stabilisation include induction of apoptosis and/or cell cycle arrest. Several studies have suggested that gamma-radiation stabilises p53 by blocking ubiquitin mediated proteolysis. Here we have compared the biological activities of p53 stabilized following exposure to gamma-radiation or treatment with the proteosome inhibitor N-acetyl-leucinyl-leucinyl-norleucinal (ALLN) in MCF7 cells with wild type p53. Stabilisation of p53 by ALLN was reversible and was not blocked by caffeine. Although ALLN was a more effective p53 stabilising agent than gamma-radiation, ALLN was not as effective at inducing cell cycle arrest/apoptosis as gamma-radiation. Although p53 stabilised by ALLN and gamma-radiation were both able to bind DNA and activate transcription, ALLN did not increase expression of BAX, which is involved in p53-induced apoptosis. Therefore, p53 stabilised by different agents is not always biologically active to the same extent and additional alterations triggered by gamma-radiation may enable p53 to activate a subset of critical target genes, such as BAX, which are required for p53 responses.
authors.affiliation: Ludwig Institute for Cancer Research, Imperial College School of Medicine, St. Mary's Campus, Norfolk Place, London, W2 1PG, UK.
authors.forename: L H
authors.initials: LH
authors.lastname: Fallis
authors.forename: E
authors.initials: E
authors.lastname: Richards
authors.forename: D J
authors.initials: DJ
authors.lastname: O'Connor
authors.forename: S
authors.initials: S
authors.lastname: Zhong
authors.forename: J K
authors.initials: JK
authors.lastname: Hsieh
authors.forename: G
authors.initials: G
authors.lastname: Packham
authors.forename: X
authors.initials: X
authors.lastname: Lu