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Monocyte-macrophage system as a target for estrogen and selective estrogen receptor modulators.

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Author

  • Pirkko Härkönen
  • H Kalervo Vaananen

Summary, in English

Postmenopausal decline of estrogen production is associated with development of several degenerative disorders such as osteoporosis, neuroinflammatory diseases and vascular wall degeneration. These are associated with the activation of the cells of the monocyte-macrophage system in a context-dependent manner. Estrogen regulates differentiation, maturation and function of many cell types in this system directly or indirectly via other cells by autocrine/paracrine mechanisms. Estrogen effects on the monocyte-macrophage system are primarily repressive. Most of these effects are mediated by repression of expression of genes for cytokines or modulation of other inflammatory mediators by the estrogen receptor (ER)-dependent or nongenomic pathways. The ER-dependent mechanisms mostly involve modulation of the nuclear factor kappa B (NF-kappaB) pathway for transcriptional regulation of cytokine or other mediator genes. In the context of hormone-regulated cancer, estrogen can influence production of cytokines or other inflammatory mediators by both tumor cells and tumor-invading macrophages. The interactions of breast and prostate cancer cells with tumor-associated macrophages (TAMs) may play an important role in tumor progression and even in the development of resistance to hormonal treatment. Regulation of the monocyte-macrophage system by estrogen and cross-talk between the ER and cytokine-mediated pathways provides multiple novel targets for development of selective ER modulator (SERM) molecules for prevention and treatment of postmenopausal degenerative and neoplastic diseases.

Publishing year

2006

Language

English

Pages

218-227

Publication/Series

Annals of the New York Academy of Sciences

Volume

1089

Issue

Nov

Document type

Journal article

Publisher

Wiley-Blackwell

Topic

  • Cancer and Oncology

Keywords

  • cancer
  • microglia
  • tumor-associated macrophage (TAM)
  • breast cancer
  • prostate
  • dendritic cell
  • osteoclast
  • selective estrogen receptor modulator
  • (SERM)
  • monocyte-macrophage system
  • estrogen
  • estrogen receptor

Status

Published

ISBN/ISSN/Other

  • ISSN: 0077-8923