mdm2 gene amplification is associated with luminal breast cancer progression in humanized PDX mice and a worse outcome of estrogen receptor positive disease.
Luminal breast cancer
humanized tumor mice
mdm2 amplification
tumor engraftment
tumor progression
Journal
International journal of cancer
ISSN: 1097-0215
Titre abrégé: Int J Cancer
Pays: United States
ID NLM: 0042124
Informations de publication
Date de publication:
15 04 2022
15 04 2022
Historique:
revised:
25
11
2021
received:
31
08
2021
accepted:
07
12
2021
pubmed:
21
12
2021
medline:
25
2
2022
entrez:
20
12
2021
Statut:
ppublish
Résumé
Estrogen receptor-positive breast cancer is a highly prevalent but heterogeneous disease among women. Advanced molecular stratification is required to enable individually most efficient treatments based on relevant prognostic and predictive biomarkers. First objective of our study was the hypothesis-driven discovery of biomarkers involved in tumor progression upon xenotransplantation of Luminal breast cancer into humanized mice. The second objective was the marker validation and correlation with the clinical outcome of Luminal breast cancer disease within the GeparTrio trial. An elevated mdm2 gene copy number was associated with enhanced tumor growth and lung metastasis in humanized tumor mice. The viability, proliferation and migration capacity of inherently mdm2 positive breast cancer cells in vitro were significantly reduced upon mdm2 knockdown or anti-mdm2 targeting. An mdm2 gain significantly correlated with a worse DFS and OS of Luminal breast cancer patients, albeit it was also associated with an enhanced preoperative pathological response rate. We provide evidence for an enhanced Luminal breast cancer stratification based on mdm2. Moreover, mdm2 can potentially be utilized as a therapeutic target in the Luminal subtype.
Substances chimiques
Receptors, Estrogen
0
MDM2 protein, human
EC 2.3.2.27
Proto-Oncogene Proteins c-mdm2
EC 2.3.2.27
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1357-1372Informations de copyright
© 2021 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.
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