Research Article Volume 116 | Issue 12 | December 2008
Retracted: G-Protein–Coupled Receptor 30 and Estrogen Receptor-α Are Involved in the Proliferative Effects Induced by Atrazine in Ovarian Cancer Cells
Atrazine, one of the most common pesticide contaminants, has been shown to up-regulate aromatase activity in certain estrogen-sensitive tumors without binding or activating the estrogen receptor (ER). Recent investigations have demonstrated that the orphan G-protein–coupled receptor 30 (GPR30), which is structurally unrelated to the ER, mediates rapid actions of 17β-estradiol and environmental estrogens.
Given the ability of atrazine to exert estrogen-like activity in cancer cells, we evaluated the potential of atrazine to signal through GPR30 in stimulating biological responses in cancer cells.
Methods and results:
Atrazine did not transactivate the endogenous ERα in different cancer cell contexts or chimeric proteins encoding the ERα and ERβ hormone-binding domain in gene reporter assays. Moreover, atrazine neither regulated the expression of ERα nor stimulated aromatase activity. Interestingly, atrazine induced extracellular signal-regulated kinase (ERK) phosphorylation and the expression of estrogen target genes. Using specific signaling inhibitors and gene silencing, we demonstrated that atrazine stimulated the proliferation of ovarian cancer cells through the GPR30–epidermal growth factor receptor transduction pathway and the involvement of ERα.
Our results indicate a novel mechanism through which atrazine may exert relevant biological effects in cancer cells. On the basis of the present data, atrazine should be included among the environmental contaminants potentially able to signal via GPR30 in eliciting estrogenic action.
Citation: Albanito L, Lappano R, Madeo A, Chimento A, Prossnitz ER, Cappello AR, Dolce V, Abonante S, Pezzi V, Maggiolini M. 2008. G-Protein–Coupled Receptor 30 and Estrogen Receptor-α Are Involved in the Proliferative Effects Induced by Atrazine in Ovarian Cancer Cells – RETRACTED. Environ Health Perspect 116:1648–1655; http://dx.doi.org/10.1289/ehp.11297
Address correspondence to M. Maggiolini, Department of Pharmaco-Biology, University of Calabria, 87030 Rende (CS), Italy. Telephone: 390984493076. Fax: 390984493458. E-mail: email@example.com
*These authors contributed equally to this work.
This research was supported by grants from the Associazione Italiana per la Ricerca sul Cancro, Ministero dell’Università e Ricerca Scientifica e Tecnologica, and Regione Calabria.
The authors declare they have no competing financial interests.
Received: 28 January 2008
Accepted: 18 July 2008
Advance Publication: 22 July 2008
This paper has been retracted. Click the following link for more information: http://dx.doi.org/10.1289/ehp.11297RET
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