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TRIM24 links glucose metabolism with transformation of human mammary epithelial cells
- 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.
- Subjects :
- Cancer Research
Glucose uptake
Cells
Nude
Clinical Sciences
Oncology and Carcinogenesis
Estrogen receptor
Mice, Nude
Breast Neoplasms
Biology
medicine.disease_cause
Cell Transformation
TRIM24
Article
Malignant transformation
Mice
Breast Cancer
medicine
Genetics
Animals
Humans
2.1 Biological and endogenous factors
Oncology & Carcinogenesis
Mammary Glands, Human
Molecular Biology
Cells, Cultured
Nutrition
Cancer
Neoplastic
Cultured
HEK 293 cells
Mammary Glands
Cell Transformation, Neoplastic
Glucose
HEK293 Cells
Anaerobic glycolysis
Cancer research
MCF-7 Cells
Ectopic expression
Female
Carcinogenesis
Carrier Proteins
Energy Metabolism
Human
Biotechnology
Subjects
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.