Study of the role of myoepitelial and stromal cells in the progression of in situ ductal carcinoma of the breast: toward novel prognostic markers

• Grant number: 12/11842-0
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: September 01, 2012
• End date: March 31, 2019
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Dirce Maria Carraro
• Grantee: Eliana Vanina Elias
• Host Institution: A C Camargo Cancer Center. Fundação Antonio Prudente (FAP). São Paulo , SP, Brazil
• Associated research grant: 13/23277-8 - Molecular aspects involved in the development and progression of breast ductal carcinoma: investigation of carcinoma in situ progression and the role of BRCA1 mutation in the triple negative tumor, AP.TEM

Abstract

Ductal carcinoma in situ (DICS) is an early lesion where the cancer cells are confined within the ducts of breast. The most feared complication of DCIS is its tendency to invade out of the confines of the ducts and become invasive cancer (IDC). It is not known what genetic changes cause DCIS to become invasive. Our laboratory has been working to characterize the gene expression pattern of the various steps of metastasis of DCIS by combining two methodologies, laser capture microdissection (LCM) and cDNA microarrays. In a previous study (Castro et al, 2008), the concept of molecular divergence was applied to independent groups of samples which mimic the progression of breast cancer [normal epithelium, pure DCIS, in situ component of lesions that coexists with invasive ductal component (IDC-DCIS) and invasive ductal carcinoma (IDC)]. The results showed that the gene expression profile of epithelial cells of the in situ component of DCIS-IDC were similar to the cells of IDC but differed from cells of pure DCIS, suggesting that genetic and molecular abnormalities, important for the acquisition of invasiveness, are already present in pre-invasive epithelial cells. Besides the role played by the epithelial cells, there is increasing evidence supporting a critical role of the microenvironment in tumor progression. Subsequently, we propose to investigate changes in gene expression pattern in both myoepithelial and fibroblast cells of two types of lesions: pure DCIS and in situ component of DCIS-IDC, where it is supposed that the molecular changes in the expression regulation are fundamental for the tumor invasion and progression. To this end, we propose the use of LCM, to isolate the myoepithelial cells and fibroblasts, combined with mRNA amplification for investigating the transcriptional alteration, by microarray and RNAseq of the microenviroment cells that surround both types of pre-invasive lesions. (AU)