Wege, Anja Kathrin and Rom-Jurek, Eva-Maria and Jank, Paul and Denkert, Carsten and Ugocsai, Peter and Solbach, Christine and Blohmer, Jens-Uwe and Sinn, Bruno and Mackelenbergh, Marion and Moebus, Volker and Trumpp, Andreas and Marangoni, Elisabetta and Pfarr, Nicole and Irlbeck, Christoph and Warfsmann, Jens and Polzer, Bernhard and Weber, Florian and Ortmann, Olaf and Loibl, Sibylle and Vladimirova, Valentina and Brockhoff, Gero (2022) mdm2 gene amplification is associated with luminal breast cancer progression in humanized PDX mice and a worse outcome of estrogen receptor positive disease. INTERNATIONAL JOURNAL OF CANCER, 150 (8). pp. 1357-1372. ISSN 0020-7136, 1097-0215
Full text not available from this repository. (Request a copy)Abstract
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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | STEM-CELL MARKERS; TUMOR-CELLS; NEW-MODEL; EXPRESSION; IDENTIFICATION; THERAPY; PROGNOSIS; SURVIVAL; CD24; P53; humanized tumor mice; Luminal breast cancer; mdm2 amplification; tumor engraftment; tumor progression |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Frauenheilkunde und Geburtshilfe (Schwerpunkt Frauenheilkunde) Medicine > Lehrstuhl für Pathologie Medicine > Lehrstuhl für experimentelle Medizin und Therapieverfahren |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 07 Sep 2022 09:06 |
| Last Modified: | 07 Sep 2022 09:06 |
| URI: | https://pred.uni-regensburg.de/id/eprint/46761 |
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