Cadmium at nanomolar concentrations activates Raf-MEK-ERK1/2 MAPKs signaling via EGFR in human cancer cell lines

Chemico-biological Interactions
Imran AliKrister Halldin

Abstract

Cadmium (Cd) is an environmental contaminant classified as carcinogenic to humans by the International Agency for Research on Cancer, supported by data from occupational exposure. Environmentally relevant dietary exposure to Cd has recently been associated with osteoporosis and cancers of the prostate, endometrium, and breast in the general population. The low exposure effects have been proposed to result from endocrine modulative properties of Cd, which mimic the physiological actions of estrogen and androgen. However, the mechanism of action of Cd is an unanswered question. We have shown previously, using mouse models, that canonical estrogen receptor signaling is not involved in estrogen mimicry effects of Cd. Instead, low-level Cd exposure stimulated the mitogen-activated protein kinases (MAPKs) ERK1/2 in these mice. Here we investigate further the ERK1/2 MAPK signaling activation by Cd in vitro by using nanomolar concentrations of cadmium chloride (CdCl2) in three different human carcinoma cell lines: HepG2, MCF-7, and ECC-1. The findings also were confirmed in previously collected mouse tissue samples. We show that 10(-8)M levels of CdCl2 activate ERK1/2 (Tyr 204) and the p53 specific ubiquitin ligase Mdm2 (Ser 166) via R...Continue Reading

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Citations

Apr 14, 2016·Toxicological Sciences : an Official Journal of the Society of Toxicology·Mary O HuffCarolyn M Klinge
Oct 26, 2016·Molecular and Cellular Endocrinology·Rosamaria LappanoMarcello Maggiolini
Dec 10, 2015·International Journal of Oncology·Hua XuTianxiang Pang
Aug 11, 2021·Toxicological Sciences : an Official Journal of the Society of Toxicology·Hsuan-Pei LinChengfeng Yang

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