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Oestrogen receptor-independent actions of oestrogen in cancer

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Abstract

Oestrogen, the primary female sex hormone, plays a significant role in tumourigenesis. The major pathway for oestrogen is via binding to its receptor [oestrogen receptor (ERα or β)], followed by nuclear translocation and transcriptional regulation of target genes. Almost 70% of breast tumours are ER + , and endocrine therapies with selective ER modulators (tamoxifen) have been successfully applied. As many as 25% of tamoxifen-treated patients experience disease relapse within 5 years upon completion of chemotherapy. In such cases, the ER-independent oestrogen actions provide a plausible explanation for the resistance, as well as expands the existing horizon of available drug targets. ER-independent oestrogen signalling occurs via one of the following pathways: signalling through membrane receptors, oxidative catabolism giving rise to genotoxic metabolites, effects on mitochondria and redox balance, and induction of inflammatory cytokines. The current review focuses on the non-classical oestrogen signalling, its role in cancer, and its clinical significance.

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  1. Department of Molecular Oncology, Cancer Institute (WIA), Adyar, Chennai, 600020, India

    Prarthana Gopinath & Gopal Gopisetty

  2. Department of Biotechnology, School of Bio and Chemical Engineering, Sathyabama Institute of Science and Technology, Chennai, 600119, India

    Revathi Paramasivam Oviya

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Gopinath, P., Oviya, R.P. & Gopisetty, G. Oestrogen receptor-independent actions of oestrogen in cancer. Mol Biol Rep 50, 9497–9509 (2023). https://doi.org/10.1007/s11033-023-08793-8

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