Tumorigenic reversion properties using 5-aza-dC and TSA on DNA methylation and breast cancer progression

Abstract

Breast cancer is a high prevalent and incident disease. Changes in the patterns of DNA methylation are related to the promotion and development of breast cancer. The patterns of methylation in elements of the apoptosis pathway are associated with disease progression, survival and metastasis. The identification of methylation changes induced by specific drugs in breast cancer cells, particularly in the cancer stem cells (CSC) population, in association with mesenchymal stem cells is unknown. The aim of this study is to research and understand gene methylation associated with apoptosis, evaluate markers in disease progression and the biological meaning of the different methylation patterns. For that, we will accomplish cells culture of specific invasive and non invasive breast cancer cells and with the co-culture with mesenchymal stem cells, evaluating the modifications in viability, apoptosis and expression modifications genes relationed with apoptosis after expose on 5 aza-dC and TSA drugs. The collaboration project with the Irma H. Russo, MD, Breast Cancer Research Laboratory (BCRL) at Fox Chase Cancer Center - Temple University Health System, directed by Jose Russo, will provide cutting edge tools and the exchange of know-how that will enable us to describe the molecular pathways that influence epigenetic effects induced by drug treatments on reversion of tumorigenic properties. The current proposal is a complement to the project "Interaction of mesenchymal stem cell with breast cancer lineage cells and evaluation of their biological behavior", FAPESP grant number 13/04659-7. (AU)