Catalan
Albanian
Arabic
Armenian
Azerbaijani
Belarusian
Bengali
Bosnian
Catalan
Czech
Danish
Deutsch
Dutch
English
Estonian
Finnish
Français
Greek
Haitian Creole
Hebrew
Hindi
Hungarian
Icelandic
Indonesian
Irish
Italian
Japanese
Korean
Latvian
Lithuanian
Macedonian
Mongolian
Norwegian
Persian
Polish
Portuguese
Romanian
Russian
Serbian
Slovak
Slovenian
Spanish
Swahili
Swedish
Turkish
Ukrainian
Vietnamese
Български
中文(简体)
中文(繁體)
Biochimica et Biophysica Acta - General Subjects 2013-Mar

Functional characterisation of p53 mutants identified in breast cancers with suboptimal responses to anthracyclines or mitomycin.

Només els usuaris registrats poden traduir articles
Inicieu sessió / registreu-vos
L'enllaç es desa al porta-retalls
Elisabet O Berge
Johanna Huun
Johan R Lillehaug
Per E Lønning
Stian Knappskog

Paraules clau

Resum

BACKGROUND

Approximately 4300 different TP53 mutations have been reported in human cancers. TP53 mutations, in particular those affecting the L2/L3 domains, are associated with resistance to anthracycline or mitomycin treatment in breast cancer patients. While many mutations have been characterised functionally, novel TP53 mutations are continuously reported. Here, we characterise 10 p53 protein variants encoded by mutated TP53 (5 within and 5 outside L2/L3) detected in locally advanced or metastatic breast cancers. Each tumour was previously characterised for response to therapy, allowing comparison between in vivo and in vitro findings.

METHODS

Mutated p53 variants were analysed for their ability to oligomerise with the wild-type protein and their subcellular localisation by immunoprecipitation and immunofluorescence, respectively. Their ability to induce transcription of target genes was determined by qPCR. Cellular growth rate, apoptosis and senescence were monitored by WST-1, TUNEL and beta-galactosidase assays, respectively.

RESULTS

Immunoprecipitation assays revealed each mutant protein to retain binding capacity for wild-type p53, thus potentially acting in a dominant negative manner. Even though each p53 variant located predominantly in the nucleus, the percentage of cells with only nuclear p53 localisation varied between 60% and 90%. None of the p53 variants were able to induce target genes to levels similar to wild-type p53, nor where they able to reduce cellular growth rate, induce apoptosis or senescence similar to wild-type p53 after anthracycline treatment in vitro.

CONCLUSIONS

All the 10 variants studied displayed inferior p53 functionality compared to the wild-type protein.

CONCLUSIONS

Our data add further information characterising the effects of somatic TP53 mutations on p53 protein function and anthracycline resistance in breast cancer.

Uneix-te a la nostra
pàgina de Facebook

La base de dades d’herbes medicinals més completa avalada per la ciència

  • Funciona en 55 idiomes
  • Cures a base d'herbes recolzades per la ciència
  • Reconeixement d’herbes per imatge
  • Mapa GPS interactiu: etiqueta les herbes a la ubicació (properament)
  • Llegiu publicacions científiques relacionades amb la vostra cerca
  • Cerqueu herbes medicinals pels seus efectes
  • Organitzeu els vostres interessos i estigueu al dia de les novetats, els assajos clínics i les patents

Escriviu un símptoma o una malaltia i llegiu sobre herbes que us poden ajudar, escriviu una herba i vegeu malalties i símptomes contra els quals s’utilitza.
* Tota la informació es basa en investigacions científiques publicades

Google Play badgeApp Store badge