Estrogen activated ers are the chief genetic safeguards of somatic and reproductive health in mammalians

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

In healthy individuals, the incessant activity of regulatory genetic mechanisms ensures the metabolic and proliferative equilibrium of cellular activity. In case of accidental defects occurring in any part of the system, a coordinated counteraction of numerous mediators may successfully help in the restoration of physiologic processes by means of either overexpression or hyperactivity. Even serious defects of genome stabilizer mechanisms may be kept in balance for a long duration, showing the clinical signs of good health. By contrast, due to the exhaustion of the compensatory processes, DNA defects may develop and lead to the clinical manifestations of diseases. Estrogen activated estrogen receptors (ERs) are the primary initiators and organizers of the upregulatory circle of genome stabilization in correlation and crosstalk with aromatase enzyme and genome safeguarding proteins, such as BRCAs. The promoter regions of ESR1, BRCA1, and CYP19 aromatase genes exhibit strong triangular partnership for the harmonized regulation of the synthesis of ERs, BRCA proteins and aromatase enzyme, which can be reconstructed from the meticulous details of earlier scientific results. Considering the extreme capacities of ER-signaling for self-restoration, it is obvious that antiestrogen treatment, either ER binding by a false ligand or inhibition of estrogen synthesis, may provoke extreme compensatory actions in genetically proficient cases. Analyses of the results of genetic studies on tumor cells have shown that upregulation of ER-signaling induced by natural estrogen or antiestrogen is a beneficial defensive process even in tumor cells, promoting their domestication and elimination. A schematic representation of the main stream of upregulative genome stabilizing circle visualizes the possibilities for extreme counteractions against the toxic effects of antiestrogens. The presented complex genome stabilizer mechanisms reveal that cancer cells may preserve their residual capacity for the upregulation of ER-signaling, even if the efforts are not satisfactory.

Original languageEnglish
Title of host publicationAdvances in Genetics Research
PublisherNova Science Publishers, Inc.
Pages53-77
Number of pages25
Volume18
ISBN (Electronic)9781536132656
ISBN (Print)9781536132649
Publication statusPublished - Jan 1 2018

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Keywords

  • Activating mutations
  • antiestrogen resistance
  • Apoptotic tumor cell death
  • Artificial estrogens
  • Breast cancer
  • Cancer prevention
  • Cancer therapy
  • DNA-repair
  • Estrogen therapy
  • Long non-coding RNAs

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Suba, Z. (2018). Estrogen activated ers are the chief genetic safeguards of somatic and reproductive health in mammalians. In Advances in Genetics Research (Vol. 18, pp. 53-77). Nova Science Publishers, Inc..