The pesticide chlorpyrifos induces estrogen receptor alpha-dependent and -independent cell signaling pathways in the breast cancer cell line MCF-7.

CLARA VENTURA, ; MARIA ROSA RAMOS NIETO, ; NOELIA MIRET, ; ANDREA RANDI, ; MARIEL NÚÑEZ, .; CLAUDIA COCCA.

Congreso; LXI Reunión Científica Anual de la Sociedad Argentina de Investigación Clínica; 2016

Chlorpyrifos (CPF) is one of the most widely used pesticides worldwide. We demonstrated that relevant environmental concentrations of CPF induce /CF breast cancer cell proliferation via estrogen receptor alpha (ERα) phosphorylation. However,there are not evidences indicating if CPF activates another cell signaling pathways that lead to E4α phosphorylation. 1bjective1ur aim Yas to study the effect of C2F on cell signaling relatedto ERα and the role on C2Finduced cell proliferation in /CFcells. /ethods Cells Yere exposed to C2F . or z/ fordifferent periods. 2rotein phosphorylation Yas assayed by 9estern$lot using specific antibodies or by immunoprecipitation andblotting using antiphosphotyrosine antibody. Cell proliferation Yasmeasured using mitotic index after h of exposure. cS4C andERα participation Yas evaluated using specific inhibitors z/22 or n/ +C+ ,, respectively. 4esults 9e observed aslight increment of tyrosine phosphorylation of cS4C inducedby . z/ C2F after h of exposure, hoYever, cell proliferationinduced by this concentration of the pesticide could not be revertedby 22. 9e have also detected an increment of E-subunit+nsulinliMe groYth factor receptor +)F4E phosphorylationpromoted by . z/ C2F until minutes of exposure p..An increment of the +)F4substrate +4S expression Yas alsodetected after h of exposure to . z/ C2F p.. All theseactions Yere abolished by +C+ ,. Furthermore, Ye found anincrement of serine phosphorylation of )S-E induced by .z/ C2F after p,, p, and p, minutesof exposure. +nterestingly, this action Yas not impeded by +C+,. Conclusions 1ur results indicate that . z/ C2F isable to activate different cell pathYays as +)F+4 signaling, Yhichcould be associated to the estrogenic action of the pesticide, andthe )S-E signaling Yhich Yould not be E4α-related.