Expression levels of MDM2 and MDMX proteins and their associated effects on P53 in human liposarcomas

摘要: Background: Inactivation of wild type P53 by its main cellular inhibitors, MDM2 and MDMX, is a well-recognised feature tumour formation in liposarcomas (LS). over-expression has been detected approximately 80% liposarcomas, but only limited information available about MDMX expression levels. On commencing this work, we were not aware any study that had described the patterns co-expression liposarcomas. Such become more pertinent as various novel / or single dual affinity antagonist compounds have emerged alternative approaches for potential targeted therapeutic strategies LS. Methods: After appropriate optimisation confirmation experimental techniques, case series 64 pathologically characterised sub-types was analysed immunohistochemistry, to simultaneously assess levels P53, MDMX. mutation status investigated cases over-expressed P53. Results: 83% 69% co-expressed at varying relative The two proteins with respect each other subtype-dependent. This apparently affected directly, distinct patterns. Diminished observed when significantly higher relation suggesting dominant role degradation P53. Higher noted increasing levels, an interaction between resulted reduced efficiency degrading No increased incidence mutations compared general population LSs. Conclusions: results indicated complex dynamic interactions may directly affect human suggests careful characterisation all these markers will be necessary considering vivo evaluation MDM blocking strategy restore functions.