Down regulation of estrogen receptors (ER a ; ER β ) and atypical chemokine receptors (ACKR 2; ACKR3; ACKR4) to increase 17β-estradiol (E2) levels in MCF-7 in-vitro study

Shruti  Talashi

doi:10.18502/bccr.v15i3.18743

Shruti Talashi Institute of Biomedical & Environmental Health Research University of the West of Scotland, Paisley Campus High street PA2 1BE, UK

DOI: https://doi.org/10.18502/bccr.v15i3.18743

Keywords: E2 – 17 β-estradiol, ACKRs – atypical chemokine receptors ER a - estrogen receptor alpha, estrogen receptor beta, RT-qPCR – real-time quantitative polymerase chain reaction.

Abstract

Background: Oestrogen plays a vital role in breast development and is strongly re- lated to breast cancer. This research article delves into this paradox. Inflammation is a cancer hallmark that involves chemokines that attract inflammatory immune cells and promote breast cancer spread. E2 as a potential estrogen can inhibit chemok- ine secretion, although the underlying mechanism remains unclear. Interestingly, atypical chemokine receptors (ACKRs), as anti-inflammatory G protein-independ- ent transmembrane proteins, act as “scavengers,” removing excessive chemokines, resulting in reduced inflammation, and most strikingly, these genes are essential for normal breast development. This finding suggested that ACKRs may act as tumour suppressors. This study investigated whether a higher E2 level can influence the ex- pression of its own receptor type and ACKRs.

Methods: In this research, a relative gene expression study has been carried out on target genes estrogen receptors (ER a, ER β) and atypical chemokine receptors (ACKR2, ACKR3 & ACKR4) normalized with TOP1 endogenous control gene in MCF-7 breast cancer cells when treated with a higher E2 level including controls for calibration using RT-qPCR technique in designing the experimental assay.

Conclusion: These findings highlight the seemingly contradictory roles of E2. While it can fuel tumour growth, it might also have anti-inflammatory effects through cross-talk with expressed ACKR genes. A study with an extended time of E2 expo- sure on MCF-7 is further proposed to assess its effect at cellular level and an auxil- iary analysis at protein level can strengthen the possibility of ERs-ACKRs interplay. Research & development in protein receptors field are valuable for evolving novel cancer therapies.

Trial Registration: Not applicable