The biological response of MCF7 breast cancer cells to proteosome inhibition or gamma-radiation is unrelated to the level of p53 induction.

Journal article

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: Fallis, L; Richards, E; O'Connor, D; Zhong, S; Hsieh, J

• Publication status: Published
• Journal: Apoptosis : an international journal on programmed cell death
• Volume: 4
• Issue: 2
• Pages: 99-107
• Publication date: 1999-04-01
• DOI: 10.1023/a:1009614726059
• EISSN: 1573-675X
• ISSN: 1360-8185
• Language: English
• Keywords: radiation; caffeine; BAX; p53; apoptosis; cell cycle