Effects of bisphenol A exposure on the proliferation and senescence of normal human mammary epithelial cells

Abstract

The carcinogenic activity of bisphenol A (BPA) is responsible for stimulating growth in estrogen-dependent breast cancer tissues, cell lines and rodent studies. However, it is not fully understood how this compound promotes mammary carcinogenesis. In our study, we examined the effect of BPA on cellular proliferation and senescence in human mammary epithelial cells (HMEC). Exposure to BPA for 1 week at the early stage at passage 8 increased the proliferation and sphere size of HMEC at the later stage up to passage 16, suggesting that BPA has the capability to modulate cell growth in breast epithelial cells. Interestingly, the number of human heterochromatin protein-1γ positive cells, which is a marker of senescence, was also increased among BPA-treated cells. Consistent with these findings, the protein levels of both p16 and cyclin E, which are known to induce cellular senescence and promote proliferation, respectively, were increased in BPA-exposed HMEC. Furthermore, DNA methylation levels of genes related to development of most or all tumor types, such as BRCA1, CCNA1, CDKN2A (p16), THBS1, TNFRSF10C and TNFRSF10D, were increased in BPA-exposed HMEC. Our findings in the HMEC model suggested that the genetic and epigenetic alterations by BPA might damage HMEC function and result in complex activities related to cell proliferation and senescence, playing a role in mammary carcinogenesis.

Low-molecular-weight inhibitors of cell differentiation enable efficient growth of mouse iPS cells under feeder-free conditions

“…The passage process was repeated up to the 6th passage. Cell PD was obtained from the number of cells using the formula described in a previous report as follows: PD = log 2 (a/b), where 'a' is the number of the cells counted in passage and 'b' represents the number of seeded cells (Qin et al 2012). The results of PD assay are shown as means with standard deviations.…”

Endocrine disruption of the epigenome: a breast cancer link

“…Spheres treated with BPA showed increased methylation levels of key genes associated with tumor development, namely BRCA1 , CCNA1 , CDKN2A , THBS1 , TNFRSF10C and TNFRSF10D , indicating that BPA alters the epigenome in a manner that promotes proliferation, senescence and tumor development (Qin et al 2012). Additional cell line studies have demonstrated aberrant methylation of the genome resulting in upregulated DNA repair genes and downregulated pro-apoptotic genes (Fernandez et al 2012), and a unique miRNA signature in BPA-treated cells distinct from miRNAs induced by estradiol (Tilghman et al 2012).…”

Efficient Establishment of Pig Embryonic Fibroblast Cell Lines with Conditional Expression of the Simian Vacuolating Virus 40 Large T Fragment

“…The rate of cell growth was evaluated by calculating the cumulative population doubling (PD) with the formula PD = (A/B)/log 2 , where A is the number of harvested cells, and B is the number of plated cells. 8,9) SA--gal staining. The cells were fixed for 5 min with a glutaraldehyde solution (2% paraformaldehyde and 0.2% glutaraldehyde in 1 Â PBS).…”