p52-Bcl3 complex promotes cyclin D1 expression in BEAS-2B cells in response to low concentration arsenite.

Abstract

Arsenic is a well-recognized human carcinogen that causes a number of malignant diseases, including lung cancer. Previous studies have indicated that cyclin D1 is frequently over-expressed in many cancer types. It is also known that arsenite exposure enhances cyclin D1 expression, which involves NF-kappaB activation. However, the mechanism between cyclin D1 and the NF-kappaB pathway has not been well studied. This study was designed to characterize the underlying mechanism of induced cell growth and cyclin D1 expression in response to low concentration sodium arsenic (NaAsO(2)) exposure through the NF-kappaB pathway. Cultured human bronchial epithelial cells, BEAS-2B, were exposed to low concentration sodium arsenite for the indicated durations, and cytotoxicity, gene expression, and protein activity were assessed. To profile the canonical and non-canonical NF-kappaB pathways involved in cell growth and cyclin D1 expression induced by low concentration arsenite, the NF-kappaB-specific inhibitor-phenethyl caffeate (CAPE) and NF-kappaB2 mRNA target sequences were used, and cyclin D1 expression in BEAS-2B cells was assessed. Our results demonstrated that exposure to low concentration arsenite enhanced BEAS-2B cells growth and cyclin D1 mRNA and protein expression. Activation and nuclear localization of p52 and Bcl3 in response to low concentration arsenite indicated that the non-canonical NF-kappaB pathway was involved in arsenite-induced cyclin D1 expression. Moreover, we further demonstrated that p52/Bcl3 complex formation enhanced cyclin D1 expression through the cyclin D1 gene promoter via its kappaB site. The up-regulation of cyclin D1 mediated by the p52-Bcl3 complex in response to low concentration arsenite might be important in assessing the health risk of low concentration arsenite and understanding the mechanisms of the harmful effects of arsenite.

• Authors: Feng Wang, Yongli Shi, Santosh Yadav, He Wang
• Journal: Toxicology (Toxicology) Vol. 273 Issue 1-3 Pg. 12-8 (Jun 29 2010) ISSN: 1879-3185 [Electronic] Ireland
• PMID: 20420878 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Arsenites
• B-Cell Lymphoma 3 Protein
• BCL3 protein, human
• NF-kappa B p52 Subunit
• Proto-Oncogene Proteins
• Sodium Compounds
• Transcription Factors
• Cyclin D1
• sodium arsenite

Topics

• Arsenites (toxicity)
• B-Cell Lymphoma 3 Protein
• Bronchi (drug effects, metabolism)
• Cell Line
• Cell Proliferation (drug effects)
• Cyclin D1 (genetics, metabolism)
• Dose-Response Relationship, Drug
• Gene Expression (drug effects)
• Humans
• NF-kappa B p52 Subunit (metabolism)
• Proto-Oncogene Proteins (metabolism)
• Sodium Compounds (toxicity)
• Transcription Factors (metabolism)
• Translocation, Genetic (drug effects)