Determination of the Molecular Mechanisms Responsible for Abnormal CD43 Expression in Breast Cancer

摘要

Human CD43 is a large, abundant and highly charged transmembrane molecule which inhibits intercellular interaction. Normally CD43 expression is restricted to the surface of hematopoietic cells. However, primary breast cancer tumors and their metastases also exhibit CD43 expression. Despite the linkage between breast cancer and abnormal CD43 expression, the molecular mechanisms responsible for this abnormal expression have never been investigated. The goal of this project is to elucidate these mechanisms. In the first year of the project we have shown that the breast cancer cell line MCF-7 exhibits abnormal CD43 expression. In addition, we have demonstrated that in vitro the proximal promoter region directs normal expression of the CD43 gene mediated by the transcription factors Puroc and hnRNP-K. Our results demonstrate that tissue culture cell lines can be used to test novel strategies for the treatment of breast cancer based on targeting CD43. We have determined that such strategies could now include the specific manipulation of Pura and hnRNP-K expression.