Exposure to cadmium chloride influences astrocyte-elevated gene-1 (AEG-1) expression in MDA-MB231 human breast cancer cells

It is known that cadmium (Cd) is able to regulate gene expression, drastically affecting the pattern of transcriptional activity and intracellular signalization in normal and pathological human cells. We have already shown that Cd exerts a cytotoxic effect on neoplastic MDA-MB231 cells from the human breast, which is characterized by the onset of a “non-classical” apoptotic kind of death, impairment of mitochondrial activity and drastic changes in gene expression pattern. In the present study, employing a combination of conventional and differential display-PCR techniques, immunocytochemical, ELISA and Western analyses, we extended the knowledge on the transcriptional modulation exerted by the metal demonstrating that in MDA-MB231 cells 5 μM CdCl2 treatment for 96 h selectively down-regulates astrocyte-elevated gene-1 (AEG-1) and reduces the accumulation of its protein product which appears to be associated with the internal cytomembranes and also present in the nucleoplasm. In addition, due to the acknowledged role of AEG-1 in the intranuclear shuttling of NF-κB p65 subunit, we also showed that CdCl2 treatment determines the decrease of p65 amount in nuclear extracts and the down-regulation of the NF-κB downstream genes c-fos and c-jun, thus providing a new contribution to the comprehension of the intracellular molecular mechanisms implicated in Cd-breast cancer cell interactions. [Display omitted] ► AEG-1 is down-regulated in MDA-MB231 breast cancer cells exposed to 5 μM CdCl2. ► AEG-1 regulates intranuclear import of NFkB p65. ► AEG-1 is upstream c-fos and c-jun expression. ► CdCl2 decreases intranuclear p65 and down-regulates c-fos/c-jun in MDA-MB231 cells. ► AEG-1 plays a key role in CdCl2 cytotoxicity.