Collagen and prostaglandin E2 regulate aromatase expression through the PI3K/AKT/IKK and the MAP kinase pathways in adipose stromal cells

  • Authors:
    • Ting Tan
    • Lie Wang
    • Bing Wang
  • View Affiliations

  • Published online on: June 9, 2015     https://doi.org/10.3892/mmr.2015.3901
  • Pages: 4766-4772
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Abstract

Excessive local estrogen production in the breast promotes estrogen-dependent breast cancer. Aromatase is a key enzyme in estrogen biosynthesis. Aromatase inhibitors used in the treatment of breast cancer are very effective, but indiscriminately reduce estrogen synthesis in all tissues, causing major side‑effects. It is thus desirable to develop inhibitors that selectively block aromatase and estrogen production in breast cancer. To this end, it is important to identify the mechanisms by which aromatase is activated in the tumor microenvironment. Prostaglandin E2 (PGE2) and collagen are two important factors in the tumor microenvironment, which contribute to tumor development and progression. In this study, we show that collagen‑induced aromatase expression in adipose stromal cells (ASCs) was significantly reduced by inhibitors of phosphatidylinositide 3‑kinase (PI3K), IκB kinase (IKK), mitogen‑activated protein kinase kinase (MEK), c‑Jun NH2‑terminal kinase (JNK), protein kinase A (PKA), and by the knockdown of the JunB and AKT2 genes. In addition, PGE2‑induced aromatase expression was significantly inhibited by inhibitors of IKK, MEK, JNK, p38 and PKA. These results indicate that the PI3K/AKT/IKK and the mitogen‑activated protein (MAP) kinase pathways are involved in collagen‑ and PGE2‑induced aromatase expression, and also suggest that collagen and PGE2‑induced signaling pathways may crosstalk in regulating aromatase expression. This study enhances our understanding on the mechanism of regulation of aromatase expression by collagen and PGE2. Furthermore, this study provides a theoretical foundation for the development of specific inhibitors of aromatase by exploiting the signaling pathways identified herein in the context of breast cancer.
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September-2015
Volume 12 Issue 3

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Tan T, Wang L and Wang B: Collagen and prostaglandin E2 regulate aromatase expression through the PI3K/AKT/IKK and the MAP kinase pathways in adipose stromal cells. Mol Med Rep 12: 4766-4772, 2015
APA
Tan, T., Wang, L., & Wang, B. (2015). Collagen and prostaglandin E2 regulate aromatase expression through the PI3K/AKT/IKK and the MAP kinase pathways in adipose stromal cells. Molecular Medicine Reports, 12, 4766-4772. https://doi.org/10.3892/mmr.2015.3901
MLA
Tan, T., Wang, L., Wang, B."Collagen and prostaglandin E2 regulate aromatase expression through the PI3K/AKT/IKK and the MAP kinase pathways in adipose stromal cells". Molecular Medicine Reports 12.3 (2015): 4766-4772.
Chicago
Tan, T., Wang, L., Wang, B."Collagen and prostaglandin E2 regulate aromatase expression through the PI3K/AKT/IKK and the MAP kinase pathways in adipose stromal cells". Molecular Medicine Reports 12, no. 3 (2015): 4766-4772. https://doi.org/10.3892/mmr.2015.3901