Effects of atrazine on estrogen receptor α- and G protein-coupled receptor 30-mediated signaling and proliferation in cancer cells and cancer-associated fibroblasts.
Effects of atrazine on estrogen receptor α- and G protein-coupled receptor 30-mediated signaling and proliferation in cancer cells and cancer-associated fibroblasts.
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DOI：
10.1289/ehp.1408586
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发表时间：
2015-05
影响因子：
10.4
通讯作者：
Maggiolini M
中科院分区：
文献类型：
--
作者：
Albanito L;Lappano R;Madeo A;Chimento A;Prossnitz ER;Cappello AR;Dolce V;Abonante S;Pezzi V;Maggiolini M
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 ERα or chimeric proteins that encode the ERα and ERβ 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 ERα expression. As a biological counterpart, atrazine stimulated the proliferation of ovarian cancer cells that depend on GPER and ERα, 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. Citation: Albanito L, Lappano R, Madeo A, Chimento A, Prossnitz ER, Capello AR, Dolce V, Abonante S, Pezzi V, Maggiolini M. 2015. Effects of atrazine on estrogen receptor α– and G protein–coupled receptor 30–mediated signaling and proliferation in cancer cells and cancer-associated fibroblasts. Environ Health Perspect 123:493–499; http://dx.doi.org/10.1289/ehp.1408586
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影响因子：
3.7
作者：
Dudek, Peter;Picard, Didier
通讯作者：
Picard, Didier
影响因子：
11.2
作者：
Madeo, Antonio;Maggiolini, Marcello
通讯作者：
Maggiolini, Marcello
影响因子：
4.1
作者：
Prossnitz ER;Barton M
通讯作者：
Barton M
DOI：
10.1186/bcr3096
发表时间：
2012-01-17
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Lappano R;Santolla MF;Pupo M;Sinicropi MS;Caruso A;Rosano C;Maggiolini M
通讯作者：
Maggiolini M
影响因子：
10.4
作者：
Pupo M;Pisano A;Lappano R;Santolla MF;De Francesco EM;Abonante S;Rosano C;Maggiolini M
通讯作者：
Maggiolini M