Email updates

Keep up to date with the latest news and content from Molecular Cancer and BioMed Central.

Open Access Research

Cadmium down-regulates expression of XIAP at the post-transcriptional level in prostate cancer cells through an NF-κB-independent, proteasome-mediated mechanism

Konstantin Golovine, Peter Makhov, Robert G Uzzo, Alexander Kutikov, David J Kaplan, Eric Fox and Vladimir M Kolenko*

Author Affiliations

Division of Urological Oncology, Department of Surgery, Fox Chase Cancer Center, Philadelphia, PA 19111, USA

For all author emails, please log on.

Molecular Cancer 2010, 9:183  doi:10.1186/1476-4598-9-183

Published: 9 July 2010

Abstract

Background

Cadmium has been classified as a human carcinogen, affecting health through occupational and environmental exposure. Cadmium has a long biological half-life (>25 years), due to the flat kinetics of its excretion. The prostate is one of the organs with highest levels of cadmium accumulation. Importantly, patients with prostate cancer appear to have higher levels of cadmium both in the circulation and in prostatic tissues.

Results

In the current report, we demonstrate for the first time that cadmium down-regulates expression of the X-linked inhibitor of apoptosis protein (XIAP) in prostate cancer cells. Cadmium-mediated XIAP depletion occurs at the post-transcriptional level via an NF-κB-independent, proteasome-mediated mechanism and coincides with an increased sensitivity of prostate cancer cells to TNF-α-mediated apoptosis. Prolonged treatment with cadmium results in selection of prostate cancer cells with apoptosis-resistant phenotype. Development of apoptosis-resistance coincides with restoration of XIAP expression in cadmium-selected PC-3 cells.

Conclusions

Selection of cadmium-resistant cells could represent an adaptive survival mechanism that may contribute to progression of prostatic malignancies.