Cytoplasmic p53β Isoforms Are Associated with Worse Disease-Free Survival in Breast Cancer

Luiza Steffens Reinhardt, Kira Groen, Brianna C. Morten, Jean-Christophe Bourdon, Kelly A. Avery-Kiejda (Lead / Corresponding author)

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Abstract

TP53 mutations are associated with tumour progression, resistance to therapy and poor prognosis. However, in breast cancer, TP53s overall mutation frequency is lower than expected (~25%), suggesting that other mechanisms may be responsible for the disruption of this critical tumour suppressor. p53 isoforms are known to enhance or disrupt p53 pathway activity in cell-and context-specific manners. Our previous study revealed that p53 isoform mRNA expression correlates with clinicopathological features and survival in breast cancer and may account for the dysregulation of the p53 pathway in the absence of TP53 mutations. Hence, in this study, the protein expression of p53 isoforms, transactivation domain p53 (TAp53), p53β, ∆40p53, ∆133p53 and ∆160p53 was analysed using immunohistochemistry in a cohort of invasive ductal carcinomas (n = 108). p53 isoforms presented distinct cellular localisation, with some isoforms being expressed in tumour cells and others in infiltrating immune cells. Moreover, high levels of p53β, most likely to be N-terminally truncated β variants, were significantly associated with worse disease-free survival, especially in tumours with wild-type TP53. To the best of our knowledge, this is the first study that analysed the endogenous protein levels of p53 isoforms in a breast cancer cohort. Our findings suggest that p53β may be a useful prognostic marker.

Original languageEnglish
Article number6670
Number of pages20
JournalInternational Journal of Molecular Sciences
Volume23
Issue number12
DOIs
Publication statusPublished - 15 Jun 2022

Keywords

  • Breast Neoplasms/genetics
  • Disease-Free Survival
  • Female
  • Humans
  • Mutation
  • Progression-Free Survival
  • Protein Isoforms/genetics
  • Tumor Suppressor Protein p53/metabolism
  • breast cancer
  • disease-free survival
  • p53 isoforms
  • ∆133p53β
  • TP53 mutation status

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