|
KMID : 1134120160190020122
|
|
Journal of Breast Cancer
2016 Volume.19 No. 2 p.122 ~ p.132
|
|
|
Role of STAT3 Phosphorylation in Ethanol-Mediated Proliferation of Breast Cancer Cells
|
|
Poornima devi Narayanan
Sangeetha Kadapakkam Nandabalan
Lakshmi Subhadra Baddireddi
|
|
|
Abstract
|
|
|
Purpose: In this study, we investigated the molecular mechanism involved in ethanol (EtOH)-mediated proliferation of breast cancer cells.
Methods: EtOH concentration was optimized by studying its effect on cell proliferation in MCF-7 and MDA MB-231 cells. We used flow cytometry and immunoblot analysis to evaluate the increased proliferation caused by the optimized concentrations of EtOH. The mechanism of EtOH-mediated proliferation was determined using reactive oxygen species (ROS) release assay, reverse transcription polymerase chain reaction, and immunoblot studies. Gene silencing followed by quantitative real-time polymerase chain reaction studies and inhibitor studies indicated the involvement of signal transducer and activator of transcription 3 (STAT3) in EtOH-mediated breast cancer proliferation.
Results: Exposure to EtOH caused an increase in cell proliferation and an accumulation of cells in S-phase in MCF-7 (347 μM EtOH) and MDA MB-231 (173 μM EtOH) cells. Additionally, increased release of ROS and the expression of pro-inflammatory cytokines, such as interleukin 6 and tumor necrosis factor α, confirmed that the proliferation was induced by the ROS-linked inflammatory response in breast cancer. The proinflammatory response was followed by phosphorylation of STAT3. The importance of STAT3 activation in EtOH-mediated proliferation was confirmed through the silencing of STAT3, followed by an investigation on the expression of cyclins and matrix metalloproteinases. Finally, studies using specific inhibitors indicated that the EtOH-mediated effect on STAT3 activation could be regulated by phosphoinositide-3-kinase and Janus kinase 2.
Conclusion: The study demonstrates the involvement of STAT3 signaling in EtOH-mediated breast cancer proliferation.
|
|
|
KEYWORD
|
|
|
Breast neoplasms, Cell proliferation, Ethanol, Inflammation
|
|
|
FullTexts / Linksout information
|
|
|
|
|
Listed journal information
|
|
   
|