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TRIM24 links glucose metabolism with transformation of human mammary epithelial cells

Authors :
Jannik N. Andersen
Mong Hong Lee
Meir J. Stampfer
T. N. Pathiraja
Kaushik N. Thakkar
Sabrina A. Stratton
Xiaobing Shi
Parantu K. Shah
Michelle Craig Barton
Zesheng Liu
Mihai Gagea
Liem Phan
Shiming Jiang
Source :
Oncogene, vol 34, iss 22, Pathiraja, TN; Thakkar, KN; Jiang, S; Stratton, S; Liu, Z; Gagea, M; et al.(2015). TRIM24 links glucose metabolism with transformation of human mammary epithelial cells. Oncogene, 34(22), 2836-2845. doi: 10.1038/onc.2014.220. Lawrence Berkeley National Laboratory: Retrieved from: http://www.escholarship.org/uc/item/4zb1m32j
Publication Year :
2015
Publisher :
eScholarship, University of California, 2015.

Abstract

© 2015 Macmillan Publishers Limited. Tripartite motif 24 protein (TRIM24) is a plant homeodomain/bromodomain histone reader, recently associated with poor overall survival of breast-cancer patients. At a molecular level, TRIM24 is a negative regulator of p53 levels and a co-activator of estrogen receptor. However, the role of TRIM24 in breast tumorigenesis remains largely unknown. We used an isogenic human mammary epithelial cell (HMEC) culture model, derived from reduction mammoplasty tissue, and found that ectopic expression of TRIM24 in immortalized HMECs (TRIM24 iHMECs) greatly increased cellular proliferation and induced malignant transformation. Subcutaneous injection of TRIM24 iHMECs in nude mice led to growth of intermediate to high-grade tumors in 60-70% of mice. Molecular analysis of TRIM24 iHMECs revealed a glycolytic and tricarboxylic acid cycle gene signature, alongside increased glucose uptake and activated aerobic glycolysis. Collectively, these results identify a role for TRIM24 in breast tumorigenesis through reprogramming of glucose metabolism in HMECs, further supporting TRIM24 as a viable therapeutic target in breast cancer.

Details

Database :
OpenAIRE
Journal :
Oncogene, vol 34, iss 22, Pathiraja, TN; Thakkar, KN; Jiang, S; Stratton, S; Liu, Z; Gagea, M; et al.(2015). TRIM24 links glucose metabolism with transformation of human mammary epithelial cells. Oncogene, 34(22), 2836-2845. doi: 10.1038/onc.2014.220. Lawrence Berkeley National Laboratory: Retrieved from: http://www.escholarship.org/uc/item/4zb1m32j
Accession number :
edsair.doi.dedup.....01b93d39ab902f8e4a6e1c76c7b34a76
Full Text :
https://doi.org/10.1038/onc.2014.220.