Evidences for involvement of estrogen receptor induced ERK1/2 activation in ovarian cancer cell proliferation by Cadmium Chloride

(2019) Evidences for involvement of estrogen receptor induced ERK1/2 activation in ovarian cancer cell proliferation by Cadmium Chloride. Toxicology in Vitro. pp. 184-193. ISSN 0887-2333

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Abstract

Cadmium (Cd) as a human carcinogen and one of the most toxic industrial and environmental pollutant mimics the estrogenic effects in cell proliferation. So, it might have a role in the incidence and etiology of hormone related cancers such as ovarian cancer as the most lethal gynecologic malignancy. This study aimed to evaluate the estrogenic effect and underlying mechanism of Cd in ovarian cancer cell line proliferation. OVCAR3 and SKOV3 cell lines were treated with different concentrations of CdCl2 (0- 50 mu M). Cell proliferation was analyzed using MTT and BrdU assay. To evaluate the estrogenic effect of Cd, the cells were pre-incubated with estrogen receptor (ER) antagonist ICI 182,780. The expression of ER was determined using western blotting method. Real-time RT-PCR method was used to assess c-fos, c-jun and FOX03a mRNA level. The results showed that Cd has an estrogenic proliferative effect at nM concentration range and ICI 182,780 significantly reversed the CdCl2 -induced cell proliferation. Cd also increased the expression of ERs. Cd exposure induced activation of p-ERK1/2 in these cells. Cd also intensified c-jun, c-fos, and FOXO3a mRNA expression. Taken together, the current work suggests that Cd induces ovarian cancer cell proliferation in an ER-dependent mechanism induced ERK1/2 activation pathway. Understanding of downstream targets by which Cd deregulates cell proliferation can be noteworthy to define its underlying carcinogenesis mechanism.

Item Type: Article
Keywords: cadmium ovarian cancer estrogen receptor erk1/2 low-dose cadmium breast-cancer er-alpha messenger-rna expression exposure beta transcription growth risk
Divisions: Faculty of Pharmacy and Pharmaceutical Sciences > Department of Clinical Biochemistry
Page Range: pp. 184-193
Journal or Publication Title: Toxicology in Vitro
Journal Index: ISI
Volume: 56
Identification Number: https://doi.org/10.1016/j.tiv.2019.01.015
ISSN: 0887-2333
Depositing User: Zahra Otroj
URI: http://eprints.mui.ac.ir/id/eprint/10122

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