Human bronchial epithelial BEAS-2B cells, an appropriate in vitro model to study heavy metals induced carcinogenesis

Abstract

Occupational and environmental exposure to arsenic (III) and chromium VI (Cr(VI)) have been confirmed to cause lung cancer. Mechanisms of these metals-induced carcinogenesis are still under investigation. Selection of cell lines to be used is essential for the mechanistic studies. Human bronchial epithelial BEAS-2B cells are the cells to be utilized by most of scientists. However, due to p53 missense mutation (CCG → TCG) at codon 47 and the codon 72 polymorphism (CGC → CCC) in BEAS-2B cells, its usage has frequently been questioned. The present study has examined activity and expression of 53 and its downstream target protein p21 upon acute or chronic exposure of BEAS-2B cells to arsenic and Cr(VI). The results show that short-term exposure of BEAS-2B cells to arsenic or Cr(VI) was able to activate both p53 and p21. Chronic exposure of BEAS-2B cells to these two metals caused malignant cell transformation and tumorigenesis. In arsenic-transformed BEAS-2B cells reductions in p53 promoter activity, mRNA expression, and phosphorylation of p53 at Ser392 were observed, while the total p53 protein level remained the same compared to those in passage-matched parent ones. p21 promoter activity and expression were decreased in arsenic-transformed cells. Cr(VI)-transformed cells exhibit elevated p53 promoter activity, mRNA expression, and phosphorylation at Ser15, but reduced phosphorylation at Ser392 and total p53 protein level compared to passage-matched parent ones. p21 promoter activity and expression were elevated in Cr(VI)-transformed cells. These results demonstrate that p53 is able to respond to exposure of arsenic or Cr(VI), suggesting that BEAS-2B cells are an appropriate in vitro model to investigate arsenic or Cr(VI) induced lung cancer.

The impact of oil spill to lung health—Insights from an RNA-seq study of human airway epithelial cells

“…We chose this particular model system also because it has been previously shown that environmental exposures can induce cell transformation of these cells (Lu et al 2015; Park et al 2015; Son et al 2012; Vales et al 2015; Zhang et al 2012). The BEAS-2B cells have been used for about 30 years in various biomedical research studies, including toxicological studies that tested chemicals, including organic, inorganic and particular agents (Fuentes-Mattei et al 2010; Garcia-Canton et al 2013; Lansley 2015; Rodrigues et al 2009; Steerenberg et al 1998; Sun et al 1995; Verstraelen et al 2014).…”

“…Importantly, compared with the air-liquid interface cell exposure (ALICE) system, submerged culture system is more suitable for modeling chronic exposure (Herzog et al 2014), as the oil pollutants exposure scenario in our study. We did not use KGM but used DMEM as the culture medium because we carefully followed the culture medium condition (DMEM) that was previously reported for studying exposure-induced malignant transformation of the BEAS-2B cells (Huang et al 2015; Kim et al 2015; Liu et al 2014; Park et al 2015; Son et al 2012; Stueckle et al 2012). In addition, numerous studies (e.g., (Dieudonne et al 2012; Jahn et al 2000; Kaur et al 2008; Skuland et al 2014)) have used BEAS-2B cells cultured in DMEM as a model for airway epithelium.…”

Induction of Slug by Chronic Exposure to Single-Walled Carbon Nanotubes Promotes Tumor Formation and Metastasis

“…1 This cell model has been reported as an appropriate model for in vitro lung carcinogenesis studies. 23,24 BSW cells were maintained in Dulbecco’s modified Eagle’s medium (DMEM) supplemented with 5% fetal bovine serum (FBS), 2 mM L-glutamine, 100 units/mL penicillin, and 100 μ g/mL streptomycin (Gibco, Gaithersburg, MA). Cells were grown at 37 °C in a humidified 95% air/5% CO 2 incubator.…”

Identification of apoptosis‐associated protein factors distinctly expressed in cigarette smoke condensate‐exposed airway bronchial epithelial cells

“…Recently, more attention has been paid to an in vitro model, using BEAS‐2B cells. This cell line is commonly used for exogenous chemical toxicity studies to examine the mechanisms involved in toxicity [13,14] …”