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

Background: Oestrogen plays a vital role in breast development and is strongly related to breast cancer. This research article delves into this paradox. Inflammation is a cancer hallmark that involve chemokine that attract inflammatory immune cells and promote breast cancer spread. E2 as a potential oestrogen can inhibit chemokine secretion, although the underlying mechanism remains unclear. Interestingly, atypical chemokine receptors (ACKRs), as anti-inflammatory G protein-independent transmembrane proteins, act as "scavengers," removing excessive chemokine's, 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 expression of its own receptors type and ACKRs. Method: In this research, a relative gene expression study been carried out on target genes estrogen receptors (ERa, ERb) and atypical chemokine receptors (ACKR2, ACKR3 & ACKR4) normalised 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. Result: Research outcome consistently revealed a down regulation in the m-RNA expression level of target genes at 18 h time point with statistical analysis done using nonparametric Mann‒Whitney's U-test confirming significant differences between the E2-treated and untreated groups (p < 0.05), supporting the hypothesis that E2 does modulates the expression of ACKR2, ACKR3 and ACKR4 via interplay with ERs. 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 exposure on MCF-7 is further proposed to assess its effect at cellular level and an auxiliary 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.