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Published VersionCC BY-NC V4.0, Open Access
Journal article
Portable NMR for the investigation of models of mammographic density ex vivo: Androgens antagonise the promotional effect of oestrogen
Biomedical Spectroscopy and Imaging, Vol.10(3-4), pp.77-97
2023
Abstract
BACKGROUND: Increased mammographic density (MD) is a strong and independent risk factor for breast cancer. Lifetime oestrogenic exposure is associated with increased MD, however androgenic effects on MD have not been widely investigated.
METHODS: We studied the effect of 17 ss-oestradiol (E2) alone or in combination with an androgen receptor (AR) agonist (5a-dihydrotestosterone [DHT]) or a selective AR modulator (Enobosarm), in modulating MD as measured via single-sided Portable NMR in a patient-derived explant (PDE) model of normal human mammary tissue.
RESULTS: We observed an upward trend in explants treated with E2 alone in 3/6 cases, an effect which appeared to be somewhat influenced by menopausal status. Co-treatment of E2 with the AR agonists DHT or Enobosarm however effected a downward trend in regards to MD. E2 significantly upregulated the ER regulated genes (ERGs) CELSR2 and AR, and the AR regulated genes SEC14L2 and GRPC5A, whereas E2 in combination with AR agonist Enobosarm downregulated ERGs SERPINA3, ATP6V1B1, TFF1 and PR regulated gene RANK. Only GREB1 and CLIC6 were upregulated by E2 and downregulated by the combination of E2 with Enobosarm. DHT + E2 exhibited no significant difference in expression of ER, AR or PR genes examined, compared with the effect of E2 alone. A negative trend was observed between ER protein levels and MD increase in PDEs. Since ER protein gets degraded upon hormone activation, this observation supports active ER signalling in the promotion of MD.
CONCLUSIONS: Collectively, these findings supports the utility of single-sided Portable NMR for the measurement ofMD in explanted human mammary tissue to detect MD change in response to exogenous hormone treatments. A mechanism through which activation of AR may reduce MD as a potential mechanism for reducing breast cancer risk associated to high MD is discussed.
Details
- Title
- Portable NMR for the investigation of models of mammographic density ex vivo: Androgens antagonise the promotional effect of oestrogen
- Authors
- Xuan Huang (Author) - Queensland University of TechnologyGina Reye (Author) - Queensland University of TechnologyKonstantin I. Momot (Corresponding Author) - Queensland University of TechnologyTony Blick (Author) - Queensland University of TechnologyThomas Lloyd (Author) - Princess Alexandra HospitalWayne D. Tilley (Author) - The University of AdelaideTheresa E. Hickey (Author) - The University of AdelaideCameron E. Snell (Author) - The University of QueenslandErik W. Thompson (Author) - Queensland University of TechnologyHonor J. Hugo (Author) - University of the Sunshine Coast, Queensland, School of Health and Behavioural Sciences - Legacy
- Publication details
- Biomedical Spectroscopy and Imaging, Vol.10(3-4), pp.77-97
- Publisher
- IOS Press
- Date published
- 2023
- DOI
- 10.3233/BSI-230000
- ISSN
- 2212-8808; 2212-8794
- Copyright note
- © 2021/2023 – The authors. Published by IOS Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (CC BY-NC 4.0).
- Grant note
- This study was funded by the Princess Alexandra Research Foundation Research Innovation Award. The Translational Research Institute receives support from the Australian Government.
- Organisation Unit
- School of Health and Behavioural Sciences - Legacy
- Language
- English
- Record Identifier
- 991064797302621
- Output Type
- Journal article
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