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Adrenomedullin is a key Protein Mediating Rotary Cell Culture System that Induces the Effects of Simulated Microgravity on Human Breast Cancer Cells

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Abstract

Microgravity or simulated microgravity promotes stem cell proliferation and inhibits differentiation. But, researchers have not yet been able to understand the underlying mechanism through which microgravity or simulated microgravity brings about stem cell proliferation and inhibition of differentiation. In this study, we investigated the effect of simulated microgravity (SMG) on MDA-MB-231 and MCF-7 human breast cancer cells using rotary cell culture system (RCCS). SMG induced a significant accumulation of these cancer cells in S phase of the cell cycle. But, compared with the static group, there was no effect on the overall growth rate of cells in the RCCS group. Furthermore, the expression of cyclin D1 was inhibited in the RCCS group, indicating that RCCS induced cell cycle arrest. In addition, RCCS also induced glycolytic metabolism by increasing the expression of adrenomedullin (ADM), but not HIF1 a. The addition of ADM further enhanced the effects of SMG, which was induced by RCCS. But, the addition of adrenomedullin antagonist (AMA) reversed these effects of SMG. Finally, our results proved that RCCS, which induced cells cycle arrest of breast cancer cells, enhanced glycolysis and upregulated the expression of ADM. But, this did not lead to an increase in hypoxia-inducible factor-1 a (HIF1 a) expression. Thus, we have uncovered a new mechanism for understanding the Warburg effect in breast cancer cells, this mechanism is not the same as hypoxia induced glycolysis.

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Acknowledgments

This work was supported by grants obtained from the National High Technology Research and Development Program of China (grant number: 2011CB710904 (http://www.most.gov.cn/eng/index.htm), which is carried out by National Natural Science Foundation of China (No. 81372813; http://www.nsfc.gov.cn/Portal0/default106.htm).

Conflict of interests

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Breast Disease Center, Southwest Hospital, Third Military Medical University, Chongqing, 400038, People’s Republic of China

    Li Chen, Xi Yang, Xiang Cui & Yu Gui

  2. Burn Research Institute, Southwest Hospital, Third Military Medical University, Chongqing, 400038, People’s Republic of China

    Li Chen, Minmin Jiang, Yanni Zhang & Xiangdong Luo

  3. National Key Laboratory of Trauma and Burns, Chongqing Key Lab. of Disease Proteomics, Chongqing, China

    Li Chen, Minmin Jiang & Xiangdong Luo

Authors
  1. Li Chen
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  2. Xi Yang
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  3. Xiang Cui
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  4. Minmin Jiang
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  5. Yu Gui
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  6. Yanni Zhang
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  7. Xiangdong Luo
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Correspondence to Xiangdong Luo.

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Chen, L., Yang, X., Cui, X. et al. Adrenomedullin is a key Protein Mediating Rotary Cell Culture System that Induces the Effects of Simulated Microgravity on Human Breast Cancer Cells. Microgravity Sci. Technol. 27, 417–426 (2015). https://doi.org/10.1007/s12217-015-9434-0

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  • DOI: https://doi.org/10.1007/s12217-015-9434-0

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