Analysis of Triple Negative Breast Cancer Based on Genes Related to Epithelial Mesenchymal Transitions

摘要

Epithelial-mesenchymal transitions (EMTs) are reversible genotypic and phenotypic transitions that occur in cells that lead to changes from epithelial to more mesenchymal-like features. One of such transitions is typical of cancer cells that change from previously polar, basal epithelial cells. The resulting changes allow for processes that favor metastasis and migration, ultimately allowing the cells to embed at secondary sites within different tissues; all factors that are typical of advanced and aggressive cancers. EMT transitions in cancer cells are a product of changes in the cellular microenvironment as well as genetic factors that influence the uncontrolled growth of the cells. Bioinformatics-based analysis of DNA microarray data generated in this laboratory showed that EMT-related genes were differentially expressed and enriched in the more aggressive, mesenchymal-like triple negative breast cancer (TNBC) cell lines compared to the less aggressive TNBCs and luminal breast cancer cells. Other investigators show that TNBC represent a heterogeneous population of patients and cell lines based on a variety of different genetic factors, but not EMT. Based on data supporting the heterogeneity of TNBC, and preliminary bioinformatics-based observations in this current laboratory that the heterogeneity of TNBCs can be distinguished based on EMT, a primary goal of this study is to validate the differential expression of EMT related genes in the more aggressive mesenchymal TNBC compared to less aggressive, less mesenchymal TNBC and luminal breast cancer. Data presented here will show that a TNBC cell line previously identified as more metastaticly aggressive, representing the more mesenchymal phenotype, demonstrates a differential pattern of EMT related genes following both transcript and protein expression analyses compared to less aggressive , less mesenchymal TNBC and luminal breast cancer cell lines. Collectively, these data show a particular set of EMT-related genes differentially expressed in a subpopulation of TNBC, possibly further characterizing TNBC heterogeneity.