5616 - The effect of cortisol on methylation patterns in breast cancer cell lines

Background

Epigenetic changes are highly responsive to environmental changes, including stress. The release of stress hormones; such as glucocorticoids, in response to stress have been shown to induce epigenetic modifications in neuronal cells. However, the role of glucocorticoids on epigenetic changes underlying important processes such as cell cycle regulation, apoptosis, and proliferation in breast cancer are not yet established. Furthermore, it is not known if cortisol can induce irreversible epigenetic changes on these cellular processes and whether these changes relate to the duration of the stress response. In this study, cortisol-induced epigenetic changes and the potential involvement of DNA methylation was assessed.

Methods

We analyzed the expression levels of maintenance DNA methyltrasferase (DNMT1) in MDA-MB-231, Hs-578T, MCF7, and T47D breast cancer cell lines by real-time PCR. We also used Qiagen Epitect Methyl ll Complete PCR array for Tumour Suppressor genes to analyse the level of methylation in 94 tumour suppressor genes. The methylation level on the Long Interspersed Nuclear Element (LINE-1) was used as surrogate marker for global DNA methylation.

Results

Our results show that cortisol significantly decreased the expression of DNMT1 in the triple negative cells lines MDA-MB-231 (p < 0.005), and Hs-578T (p < 0.05). We also showed that cortisol induced aberrant methylation characterised by loss of methylation on promoter regions of key tumour suppressor genes in MDA-MB-231 cells, such as DAPK1, MGMT, AKT1, CDKN1A, and ABL1 and hypomethylation of the global genome.

Conclusions

Taken together, cortisol induced aberrant methylation patterns which may have important implications on progression of the disease.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.