Mammary-specific expression of Trim24 establishes a mouse model of human metaplastic breast cancer

Vrutant V. Shah, Aundrietta D. Duncan, Shiming Jiang, Sabrina A. Stratton, Kendra L. Allton, Clinton Yam, Abhinav Jain, Patrick M. Krause, Yue Lu, Shirong Cai, Yizheng Tu, Xinhui Zhou, Xiaomei Zhang, Yan Jiang, Christopher L. Carroll, Zhijun Kang, Bin Liu, Jianjun Shen, Mihai Gagea, Sebastian M. Manu, Lei Huo, Michael Gilcrease, Reid T. Powell, Lei Guo, Clifford Stephan, Peter J. Davies, Jan Parker-Thornburg, Guillermina Lozano, Richard R. Behringer, Helen Piwnica-Worms, Jeffrey T. Chang (), Stacy L. Moulder () and Michelle Craig Barton ()
Additional contact information
Vrutant V. Shah: The University of Texas MD Anderson Cancer Center
Aundrietta D. Duncan: The University of Texas MD Anderson Cancer Center
Shiming Jiang: The University of Texas MD Anderson Cancer Center
Sabrina A. Stratton: The University of Texas MD Anderson Cancer Center
Kendra L. Allton: The University of Texas MD Anderson Cancer Center
Clinton Yam: The University of Texas MD Anderson Cancer Center
Abhinav Jain: The University of Texas MD Anderson Cancer Center
Patrick M. Krause: The University of Texas MD Anderson Cancer Center
Yue Lu: The University of Texas MD Anderson Cancer Center
Shirong Cai: The University of Texas MD Anderson Cancer Center
Yizheng Tu: The University of Texas MD Anderson Cancer Center
Xinhui Zhou: The University of Texas MD Anderson Cancer Center
Xiaomei Zhang: The University of Texas MD Anderson Cancer Center
Yan Jiang: The University of Texas MD Anderson Cancer Center
Christopher L. Carroll: The University of Texas MD Anderson Cancer Center
Zhijun Kang: The University of Texas MD Anderson Cancer Center
Bin Liu: The University of Texas MD Anderson Cancer Center
Jianjun Shen: The University of Texas MD Anderson Cancer Center
Mihai Gagea: The University of Texas MD Anderson Cancer Center
Sebastian M. Manu: The University of Texas MD Anderson Cancer Center
Lei Huo: The University of Texas MD Anderson Cancer Center
Michael Gilcrease: The University of Texas MD Anderson Cancer Center
Reid T. Powell: Texas A&M College of Medicine
Lei Guo: Texas A&M College of Medicine
Clifford Stephan: Texas A&M College of Medicine
Peter J. Davies: Texas A&M College of Medicine
Jan Parker-Thornburg: The University of Texas MD Anderson Cancer Center
Guillermina Lozano: The University of Texas MD Anderson Cancer Center
Richard R. Behringer: The University of Texas MD Anderson Cancer Center
Helen Piwnica-Worms: The University of Texas MD Anderson Cancer Center
Jeffrey T. Chang: University of Texas
Stacy L. Moulder: The University of Texas MD Anderson Cancer Center
Michelle Craig Barton: The University of Texas MD Anderson Cancer Center

Nature Communications, 2021, vol. 12, issue 1, 1-15

Abstract: Abstract Conditional overexpression of histone reader Tripartite motif containing protein 24 (TRIM24) in mouse mammary epithelia (Trim24COE) drives spontaneous development of mammary carcinosarcoma tumors, lacking ER, PR and HER2. Human carcinosarcomas or metaplastic breast cancers (MpBC) are a rare, chemorefractory subclass of triple-negative breast cancers (TNBC). Comparison of Trim24COE metaplastic carcinosarcoma morphology, TRIM24 protein levels and a derived Trim24COE gene signature reveals strong correlation with human MpBC tumors and MpBC patient-derived xenograft (PDX) models. Global and single-cell tumor profiling reveal Met as a direct oncogenic target of TRIM24, leading to aberrant PI3K/mTOR activation. Here, we find that pharmacological inhibition of these pathways in primary Trim24COE tumor cells and TRIM24-PROTAC treatment of MpBC TNBC PDX tumorspheres decreased cellular viability, suggesting potential in therapeutically targeting TRIM24 and its regulated pathways in TRIM24-expressing TNBC.

Date: 2021
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-021-25650-z Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-25650-z

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-021-25650-z

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().