| Abstract | Cadmium (Cd), an endocrine disruptor, can induce a variety of signaling events including the activation of ERK1/2 and AKT. In this study, the involvement of estrogen receptors (ER) in these events was evaluated in three human breast cancer cell lines, MCF-7, MDA-MB-231, and SK-BR-3. The Cd-induced signal activation patterns in the three cell lines mimicked those exhibited in response to 17 beta-estradiol. Specifically, treatment of MCF-7 cells, that express ER alpha, ER beta and GPR30, to 0.5-10 microM Cd for only 2.5 min resulted in transient phosphorylation of ERK1/2. Cd also triggered a gradual increase and sustained activation of AKT during the 60 min treatment period. In SK-BR-3 cells, that express only GPR30, Cd also caused a transient activation of ERK1/2, but not of AKT. In contrast, in MDA-MB-231 cells, that express only ER beta, Cd was unable to cause rapid activation of either ERK1/2 or AKT. A transient phosphorylation of ER alpha was also observed within 2.5 min of Cd exposure in the MCF-7 cells. While the estrogen receptor antagonist, ICI 182,780, did not prevent the effect of Cd on these signals, specific siRNA against hER alpha significantly reduced Cd-induced activation of ERK1/2 and completely blocked the activation of AKT. It is concluded that Cd, like estradiol, can cause rapid activation of ERK1/2 and AKT and that these signaling events are mediated by possible interaction with membrane ER alpha and GPR30, but not ER beta. |
| Authors | Zhiwei Liu, Xinyuan Yu, Zahir A Shaikh
(Affiliation: Department of Biomedical and Pharmaceutical Science, and Center for Molecular Toxicology, College of Pharmacy, University of Rhode Island, Kingston, RI 02881, USA.)
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| Journal | Toxicology and applied pharmacology
(Toxicol Appl Pharmacol)
Vol. 228
Issue 3
Pg. 286-94
(May 1 2008)
ISSN: 0041-008X United States |
| PMID | 18275979
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
|
| Chemical References |
- Endocrine Disruptors
- Estrogen Antagonists
- MIER1 protein, human
- Nuclear Proteins
- RNA, Small Interfering
- Transcription Factors
- Cadmium
- Mitogen-Activated Protein Kinase 1
- Mitogen-Activated Protein Kinase 3
- Proto-Oncogene Proteins c-akt
|
| Topics |
- Breast Neoplasms
(metabolism, pathology)
- Cadmium
(toxicity)
- Cell Line, Tumor
- Endocrine Disruptors
(toxicity)
- Enzyme Activation
(drug effects)
- Estrogen Antagonists
(pharmacology)
- Female
- Humans
- Mitogen-Activated Protein Kinase 1
(metabolism)
- Mitogen-Activated Protein Kinase 3
(metabolism)
- Nuclear Proteins
(metabolism)
- Phosphorylation
- Proto-Oncogene Proteins c-akt
(metabolism)
- RNA, Small Interfering
(pharmacology)
- Transcription Factors
(metabolism)
|
