SIR Medicine Investigation Abstract
DEPLETION OF BRCA2 IN HUMAN MAMMARY EPITHELIAL CELLS LEADS TO EPITHELIAL-MESENCHYMAL TRANSITION (EMT)
Presenter:
Cristina Thomas, Illinois Mathematics and Science Academy
Advisor:
Dr. Qingshen Gao, Evanston Northwestern Healthcare Research Institute
Abstract:
Accumulating around 186,000 new cases and 46,000 deaths in the United States alone, breast cancer is clearly the most diagnosed cancer in women. Breast cancer deaths are primarily results of the local invasion and remote metastasis of tumor cells. Cells gain motility through the epithelial mesenchymal transition (EMT), during which cells lose intercellular adhesion. However, they are only able to undergo the invasive phase when E-cadherin is downregulated. Snail, a transcription factor, is suggested to be a direct repressor of E-cadherin during transcription. Furthermore, because increased Snail expression has been associated with the downregulation of E-cadherin, the regulation of Snail may be necessary to ensure normal epithelial cells. This study examines the possible role of BRCA2, a breast cancer susceptibility gene, in the EMT process and tumor metastasis. This research demonstrates that the knockdown of BRCA2 in cells stimulates an epithelial mesenchymal conversion with the loss of the epithelial markers E-cadherin, a-catenin, and ß-catenin, and the growth of mesenchymal markers, Vimentin and Fibronectin. Thus, the loss of BRCA2 in epithelial cells plays a major role in metastasis by generating an epithelial mesenchymal transition.