Abstract 5616
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.
Resources from the same session
5444 - Analysis of the tumor microenvironment and tumor genotype through different stages of lung adenocarcinoma
Presenter: Peter Zink
Session: Poster Display session 1
Resources:
Abstract
3124 - Does Progress achieved in the Treatment of Patients with Metastatic Non-Small-Cell Lung Cancer (NSCLC) reach the Elderly Population?
Presenter: Jorune Suipyte
Session: Poster Display session 1
Resources:
Abstract
5142 - Prognostic factors for non-small cell lung cancer patients with driver mutation negative and brain metastases (HOT 1701)
Presenter: Yoshihito Ohhara
Session: Poster Display session 1
Resources:
Abstract
1580 - A novel risk classification system based on nomogram scores to predict survival of patients presenting with brain metastases at the first diagnosis of NSCLC
Presenter: Pengfei Cui
Session: Poster Display session 1
Resources:
Abstract
4442 - Comparison of real-world response rate (rwRR) to RECIST-based response rate in patients with advanced non-small cell lung cancer (aNSCLC)
Presenter: Xinran Ma
Session: Poster Display session 1
Resources:
Abstract
5405 - Estimating the cost and survival impact of new aNSCLC therapies in Canada with the iTEN model
Presenter: Parneet Kaur Cheema
Session: Poster Display session 1
Resources:
Abstract
1893 - SMARCA4 Deficient Non-Small Cell Lung Cancer (NSCLC): A Comprehensive Genomic Profiling (CGP) Study
Presenter: Stephen Graziano
Session: Poster Display session 1
Resources:
Abstract
5582 - Exploring Resistance to Nivolumab [NIV] applying an Immune Genomic Signature (IGS) in advanced pretreated NSCLC [PRINCiPe study]
Presenter: Sara Pilotto
Session: Poster Display session 1
Resources:
Abstract
1408 - DNA damage repair deficiency is associated with early resistance to crizotinib: whole-genome analysis in non-small cell lung cancer patients with ALK-fusion
Presenter: Dongyun He
Session: Poster Display session 1
Resources:
Abstract
5751 - Phase 3 ALTA-3 study of brigatinib (BRG) vs alectinib (ALC) in patients (pts) with advanced anaplastic lymphoma kinase (ALK)−positive non–small cell lung cancer (NSCLC) that progressed on crizotinib (CRZ)
Presenter: Sanjay Popat
Session: Poster Display session 1
Resources:
Abstract