"Gene Expression Study of Inflammatory Pathways in Breast Epithelial lines MCF10F and SKBR3 Stem Cells Subpopulation after Angiotensin 1-7 Treatment"

• Grant number: 11/21360-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: January 01, 2012
• End date: December 31, 2012
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Ismael Dale Cotrim Guerreiro da Silva
• Grantee: Werica Bernardo Pereira
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Breast cancer is the most common cancer among women, accounting for thousands of deaths annually. Among the various mediators that act in the carcinogenic process, the components of the renin-angiotensin system (RAS) have assumed an important role. Angiotensin II (Ang II), better known peptide obtained from the cascade of events of RAS, has vasoconstrictive, angiogenic, hyperplastic, proliferative and metastatic. On the other hand, angiotensin-(1-7) [Ang-(1-7)] another peptide belonging to the RAS and which has been extensively studied lately, triggers vasodilator actions, antiproliferative and apoptotic effects, contrary to the ones generated by Ang II. It is known that solid tumors have a heterogeneous cellular composition and only a small portion of its cells has the capacity to proliferate and generate new tumors. Recently it has been proposed that this differential proliferation skill among cells from the same tumoric mass could be explained by the fact that only a certain cell subgroup with the primordial characteristics (cancer stem cells CSCs) could give rise to new tumors. Therefore, we propose in this study was to evaluate the role of Ang II, Ang-(1-7), estradiol and hCG in the control of genes that modulate the expression of membrane receptors related to the inflammatory response and may be differentially expressed in undifferentiated mammary epithelial subpopulation of unipotent stem cells, compared to their progeny, both in normal breast cell lines (MCF-10F) and in tumorigenic (SK-BR3). Those cell lines containing a stem cell will display subpopulation marked with ALDEFLUOR (Genestier et al., 2010), and will be separated by FACS and submitted to the following biological experiments: apoptosis, and viability (GUAVA cytometer) measurements, and gene differential expression analysis through PCR array (SA Bioscience) and qPCR (for validations).