Oestrogen receptor-independent actions of oestrogen in cancer

• Published in: Molecular biology reports Vol. 50; no. 11; pp. 9497 - 9509
• Main Authors: Gopinath, Prarthana, Oviya, Revathi Paramasivam, Gopisetty, Gopal
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01.11.2023; Springer Nature B.V
• Subjects: Animal Anatomy; Animal Biochemistry; Antibiotics; Biomedical and Life Sciences; Body fat; Brain; Breast cancer; Cell surface receptors; Chemotherapy; Cholesterol; Clinical significance; Cytochrome; Cytokines; Dehydrogenases; Endocrine therapy; Enzymes; Estrogen receptors; Estrogens; Estrogens - metabolism; Female; Gene regulation; Genotoxicity; Histology; Hormones; Humans; Inflammation; Kinases; Life Sciences; Metabolism; Metabolites; Molecular biology; Morphology; Neoplasm Recurrence, Local - drug therapy; Nuclear transport; Ovaries; Physiology; Proteins; Receptors, Estrogen - genetics; Receptors, Estrogen - metabolism; Review; Sex hormones; Signal Transduction; Tamoxifen; Tamoxifen - pharmacology; Therapeutic targets; Tumorigenesis; Tumors; Womens health; Estrogen receptor-independent signalling; Breast cancer; Tamoxifen resistance; GPER1; Estrogen metabolites
• ISSN: 0301-4851; 1573-4978
• DOI: 10.1007/s11033-023-08793-8

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.