Abstract 228: Depletion of stem-loop binding protein and elevation of polyadenylation of histone 3.1 contribute to malignant cell transformation induced by bisphenol A

Abstract

Abstract Introduction: Bisphenol A (BPA) is a pervasive chemical exposure in the US and has been linked to adverse health effects in humans and mainly identified as an endocrine disruptor. However, recent studies suggests that all plastics including our daily usages for food/drink containers may leach chemicals if they are scratched or heated or stored long term and strongly suggests that at certain exposure levels of BPA in these products, may cause cancers including breast, lung, and ovarian cancers in humans. Although there are few studies about breast, lung and ovarian cancers, with BPA exposure there is an urgent need to focus on the BPA’s carcinogenic activity in the lung. Because lung cancers can progress to life threatening events and short life span once it is diagnosed, identifying the mechanism that specifically inhibits/prevents lung cancers invasion and related morbidity is of tremendous importance for reducing mortality. Therefore, in this study, we investigated the carcinogenicity of BPA using human bronchial epithelial cells. Experimental methods: To determine whether BPA alters canonical histone mRNA processing in vitro, we measured levels of polyadenylation (polyA) of canonical histone (H)3.1 mRNA as well as protein expression of Stem-loop binding protein (SLBP), and H3 protein in human bronchial epithelial BEAS-2B cells exposed to various concentrations of BPA for 96 h. Furthermore, BEAS-2B cells were chronically exposed to low doses of BPA, the cell transformation assay was performed in an anchorage-independent growth and colony formation was assessed. Arsenic was used as a positive control because our laboratory previously demonstrated that arsenic-induced polyA of H3.1 mRNA, by depletion of SLBP in vitro and that polyA of H3.1 mRNA enhanced tumor formation in nude mice. Results: Our results showed that exposure of BEAS-2B cells to BPA depleted SLBP, induced polyA of canonical histone mRNAs, and upregulated H3 protein. The results from real-time quantitative PCR showed that BPA exposure increased level of polyA H3.1 mRNA. Furthermore, our findings from an anchorage-independent growth assay also indicate that exposure of BEAS-2B cells to low doses of BPA induced malignant cell transformation. Conclusions: The present study demonstrated that chronic exposure of the cells to BPA causes malignant cell transformation, indicating that BPA is a potent human carcinogen to induce lung cancer. Our study also demonstrated that the loss of SLBP and gain of polyA H3.1 mRNA play an important role in BPA-induced carcinogenesis. Citation Format: Arul Veerappan, Zhou Zhang, Max Costa. Depletion of stem-loop binding protein and elevation of polyadenylation of histone 3.1 contribute to malignant cell transformation induced by bisphenol A [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 228.