Dataset Information

Effects of atrazine on estrogen receptor ?- and G protein-coupled receptor 30-mediated signaling and proliferation in cancer cells and cancer-associated fibroblasts.

ABSTRACT:

Background

The pesticide atrazine does not bind to or activate the classical estrogen receptor (ER), but it up-regulates the aromatase activity in estrogen-sensitive tumor cells. The G protein estrogen receptor (GPR30/GPER) has been reported to be involved in certain biological responses to endogenous estrogens and environmental compounds exerting estrogen-like activity.

Objectives

We aimed to evaluate the potential of atrazine to trigger GPER-mediated signaling in cancer cells and cancer-associated fibroblasts (CAFs).

Methods and results

Using gene reporter assays in diverse types of cancer cells, we found that atrazine did not transactivate endogenous ER? or chimeric proteins that encode the ER? and ER? hormone binding domains. Conversely, atrazine was able to bind to GPER to induce ERK activation and the expression of estrogen target genes, which, interestingly, appeared to rely on both GPER and ER? expression. As a biological counterpart, atrazine stimulated the proliferation of ovarian cancer cells that depend on GPER and ER?, as evidenced by gene silencing experiments and the use of specific signaling inhibitors. Of note, through GPER, atrazine elicited ERK phosphorylation, gene expression, and migration in CAFs, thus extending its stimulatory role to these main players of the tumor microenvironment.

Conclusions

Our results suggest a novel mechanism through which atrazine may exert relevant biological effects in cancer cells and CAFs. On the basis of our data, atrazine should be included among the environmental contaminants that may elicit estrogenic activity through GPER-mediated signaling.

SUBMITTER: Albanito L

PROVIDER: S-EPMC4421771 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature

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Publications

Effects of atrazine on estrogen receptor α- and G protein-coupled receptor 30-mediated signaling and proliferation in cancer cells and cancer-associated fibroblasts.

Albanito Lidia L Lappano Rosamaria R Madeo Antonio A Chimento Adele A Prossnitz Eric R ER Cappello Anna Rita AR Dolce Vincenza V Abonante Sergio S Pezzi Vincenzo V Maggiolini Marcello M

Environmental health perspectives 20150116 5

<h4>Background</h4>The pesticide atrazine does not bind to or activate the classical estrogen receptor (ER), but it up-regulates the aromatase activity in estrogen-sensitive tumor cells. The G protein estrogen receptor (GPR30/GPER) has been reported to be involved in certain biological responses to endogenous estrogens and environmental compounds exerting estrogen-like activity.<h4>Objectives</h4>We aimed to evaluate the potential of atrazine to trigger GPER-mediated signaling in cancer cells an ...[more]

PMID: 25616260

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