LIVER X RECEPTOR (LXR) activation may affect breast cancer risk through induction of tristetraprolin (TTP) in mamary epithelial cells

BOGNI EMILIA; GRINMAN DIEGO; VALLONE SABRINA ; GATTELLI ALBANA; PECCI, ADALI; MEISS ROBERTO; KORDON EDITH

CABA

Simposio; BA-BCS 2021; 2021

Tristetraprolin (TTP), a protein coded by the Zfp36gene, induces mRNA degradation of proteins involvedin inflammation and tumorigenesis, while LXRa is a transcriptionfactor that plays relevant roles in cholesterol andinflammation control. Our previous data show that bothproteins are highly expressed and active in the mousemammary epithelium during lactation. Besides, it has beenproposed that a single nucleotide polymorphism, whichmay alter an LXR binding site in the human Zfp36 promoterregion, is associated with lower TTP expression and worseprognosis in breast cancer patients. In order to analyzeLXR role on TTP expression regulation in mammary cells,female mice were treated with the LXR agonist GW3965(GW) or DMSO (control) by IP injection during 96h afterweaning. Our results show that GW induced TTP, whileinhibited IL-6, TNFa, LIF and S100A9 expression in theinvoluting glands. On the other hand, we analyzed theeffects of GW as well as lactogenic hormones: glucocorticoids(Dex) and prolactin (Prl) on HC11 mouse mammarycells in culture. We found that both GW and Dex+Prlinduced TTP and B-Casein mRNA expression. However,differently from the lactogenic hormones, GW did not triggerSTAT5 phosphorylation. These results suggest thatLXR may be involved in TTP expression regulation in themammary gland through a STA5-independent mechanism.New experiments are underway to verify the impact of theLXR-TTP pathway on breast cancer progression.