期刊
ONCOLOGY REPORTS
卷 33, 期 6, 页码 2689-2694出版社
SPANDIDOS PUBL LTD
DOI: 10.3892/or.2015.3880
关键词
breast cancer; adipocytes; HIF1 alpha; estrogen receptor; epithelial-mesenchymal transition
类别
资金
- Translational Research Institute (TRI) through the NIH National Center for Research Resources [UL1TR000039]
- Translational Research Institute (TRI) through the NIH National Center for Advancing Translational Sciences
- Arkansas Breast Cancer Research Program
- NCI [1R01CA128897]
The development of breast cancer is linked to the loss of estrogen receptor (ER) during the course of tumor progression, resulting in loss of responsiveness to hormonal treatment. The mechanisms underlying dynamic ER alpha gene expression change in breast cancer remain unclear. A range of physiological and biological changes, including increased adipose tissue hypoxia, accompanies obesity. Hypoxia in adipocytes can establish a pro-malignancy environment in breast tissues. Epidemiological studies have linked obesity with basal-like breast cancer risk and poor disease outcome, suggesting that obesity may affect the tumor phenotype by skewing the microenvironment toward support of more aggressive tumor phenotypes. In the present study, human SOBS adipocytes were co-cultured with ER-positive MCF7 cells for 24 h. After co-culture, HIF1 alpha, TGF-beta, and lectin-type oxidized LDL receptor 1 (LOX1) mRNA levels in the SOBS cells were increased. Expression levels of the epithelial-mesenchymal transition (EMT)-inducing transcription factors FOXC2 and TWIST1 were increased in the co-cultured MCF7 cells. In addition, the E-cadherin mRNA level was decreased, while the N-cadherin mRNA level was increased in the co-cultured MCF7 cells. ER alpha mRNA levels were significantly repressed in the co-cultured MCF7 cells. ER alpha gene expression in the MCF7 cells was decreased due to increased HIF1 alpha in the SOBS cells. These results suggest that adipocytes can modify breast cancer cell ER gene expression through hypoxia and also can promote EMT processes in breast cancer cells, supporting an important role of obesity in aggressive breast cancer development.
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