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

TP53 mutations are associated with tumour progression, resistance to therapy and poor prognosis. However, in breast cancer, TP53′s overall mutation frequency is lower than expected (~25%), suggesting that other mechanisms may be responsible for the disruption of this critical tumour suppressor. p53...

Full description

Saved in:
Bibliographic Details
Published in:International journal of molecular sciences 2022-06, Vol.23 (12), p.6670
Main Authors: Steffens Reinhardt, Luiza, Groen, Kira, Morten, Brianna C., Bourdon, Jean-Christophe, Avery-Kiejda, Kelly A.
Format: Article
Language:English
Subjects:
Breast cancer
Carcinoma
Cytoplasm
disease-free survival
Gene expression
Immune system
Immunohistochemistry
Invasiveness
Isoforms
Localization
Medical prognosis
Mutation
p53 isoforms
p53 Protein
Proteins
Survival
TP53 mutation status
Tumor suppressor genes
Tumors
Womens health
Δ133p53β
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:TP53 mutations are associated with tumour progression, resistance to therapy and poor prognosis. However, in breast cancer, TP53′s 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, Δ40p53, Δ133p53 and Δ160p53 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.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms23126670