Estrogen Receptor-Beta2 (ERβ2)-Mutant p53-FOXM1 Axis: A Novel Driver of Proliferation, Chemoresistance, and Disease Progression in High Grade Serous Ovarian Cancer (HGSOC).
FOXM1
apoptosis
carboplatin
cell proliferation
estrogen receptor-beta2
high grade serous ovarian cancer
mutant p53
patient tumors
proximity ligation assay
therapeutic resistance
Journal
Cancers
ISSN: 2072-6694
Titre abrégé: Cancers (Basel)
Pays: Switzerland
ID NLM: 101526829
Informations de publication
Date de publication:
22 02 2022
22 02 2022
Historique:
received:
31
12
2021
revised:
08
02
2022
accepted:
17
02
2022
entrez:
10
3
2022
pubmed:
11
3
2022
medline:
11
3
2022
Statut:
epublish
Résumé
High grade serous ovarian cancer (HGSOC) is the most common and lethal subtype of epithelial ovarian cancer. Prevalence (~96%) of mutant p53 is a hallmark of HGSOC. Estrogen receptor-beta (ERβ) has been reported to be another important player in HGSOC, although the pro-versus anti-tumorigenic role of its different isoforms remains unsettled. However, whether there is functional interaction between ERβ and mutant p53 in HGSOC is unknown. ERβ1 and ERβ2 mRNA and protein analysis in HGSOC cell lines demonstrated that ERβ2 is the predominant isoform in HGSOC. Specificity of ERβ2 antibody was ascertained using cells depleted of ERβ2 and ERβ1 separately with isoform-specific siRNAs. ERβ2-mutant p53 interaction in cell lines was confirmed by co-immunoprecipitation and in situ proximity ligation assay (PLA). Expression levels of ERβ2, ERα, p53, and FOXM1 proteins and ERβ2-mutant p53 interaction in patient tumors were determined by immunohistochemistry (IHC) and PLA, respectively. ERβ2 levels correlate positively with FOXM1 levels and negatively with progression-free survival (PFS) and overall survival (OS). Quantitative chromatin immunoprecipitation (qChIP) and mRNA expression analysis revealed that ERβ2 and mutant p53 co-dependently regulated
Identifiants
pubmed: 35267428
pii: cancers14051120
doi: 10.3390/cancers14051120
pmc: PMC8909529
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : NCI NIH HHS
ID : P50 CA159981
Pays : United States
Organisme : NCRR NIH HHS
ID : S10OD019977
Pays : United States
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