Dépôt numérique
RECHERCHER

Neonicotinoids Cause a Promoter-Switch of CYP19 Expression in Hs578t Breast Cancer Cells by Activating the VEGF-Signaling Pathways: What Are the Implications for Breast Cancer?

Caron-Beaudoin, Elyse; Viau, Mélanie; Sanderson, J. Thomas . Neonicotinoids Cause a Promoter-Switch of CYP19 Expression in Hs578t Breast Cancer Cells by Activating the VEGF-Signaling Pathways: What Are the Implications for Breast Cancer? In: Society of Toxicology (SOT), 56th annual meeting, 12-16 mars 2017, Baltimore.

Ce document n'est pas hébergé sur EspaceINRS.

Résumé

Aromatase (CYP19) is a key enzyme in the biosynthesis of estrogen and is expressed in a promoter-specific manner. In the healthy mammary gland, CYP19 is expressed at low levels under the regulation of its I.4 promoter. In hormone-dependent breast cancer, fibroblast cells surrounding the tutor have increased CYP19 expression due to a mechanism of promoter-switch usage, leading to inhibition of normal I.4 promoter activity and an increase of the activities of the PII, I.3 and I.7-promoters. The final outcome is an overproduction of estrogens in the tutor microenvironment. Little is known about the effects of environmental chemicals on the promoter-specific expression of CYP19, but exposure to certain endocrine disruptors may increase the risk of developing breast cancer. We determined the effects of two widely used neonicotinoids (thiacloprid and imidacloprid) on the promoter-specific expression of CYP19 in Hs578t breast cancer cells. We are the first to demonstrate that the normal I.4 promoter of CYP19, and its breast cancer-related PII, I.3 and I.7 promoters are active in this cell line. We found that the expression of CYP19 via the PII, I.3 and I.7 promoters in Hs578t is dependent on the activation of two VEGF singling pathways (MAPK 1/3 and phospholipase C (PLC)). Exposure of Hs578t cells to environmentally relevant concentrations of imidacloprid and thiacloprid resulted in a switch in CYP19 promoter usage, involving a strong inhibition of normal I.4 promoter activity, whereas PII, I.3 and I.7 promoter-mediated CYP19 expression was strongly increased, leading to an overall induction of aromatase catalytic activity. We determined that thiacloprid and imidacloprid exert their effects by stimulating the MAPK 1/3 and PLC pathways. This unique change in promoter usage is usually observed in patients with progressive hormone-dependent breast cancer and we are the first to show that certain neonicotinoids may be able to trigger or stimulate this process in vitro.

Type de document: Document issu d'une conférence ou d'un atelier
Informations complémentaires: The Toxicologist 156:149. Abstract #1635
Mots-clés libres: -
Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 10 sept. 2018 20:49
Dernière modification: 10 sept. 2018 20:49
URI: http://espace.inrs.ca/id/eprint/7520

Actions (Identification requise)

Modifier la notice Modifier la notice