Breast cancer has a high incidence and mortality rate worldwide. Several viral vectors including lentiviral, adenoviral and adeno-associated viral vectors have been used in gene therapy for various forms of human
cancer, and have shown promising effects in controlling
tumor development. Claudin1 (CLDN1) is a member of the tetraspan transmembrane
protein family that plays a major role in tight junctions and is associated with
tumor metastasis. However, the role of CLDN1 in
breast cancer is largely unexplored. In this study, we tested the therapeutic potential of silencing CLDN1 expression in two
breast cancer (MDA-MB-231 and MCF7) cell lines using lentiviral vector mediated RNA interference. We found that a CLDN1 short hairpin (
shRNA) construct efficiently silenced CLDN1 expression in both
breast cancer cell lines, and CLDN1 knockdown resulted in reduced cell proliferation, survival, migration and invasion. Furthermore, silencing CLDN1 inhibited epithelial to mesenchymal transition (EMT) by upregulating the epithelial cell marker,
E-cadherin, and downregulating mesenchymal markers, smooth muscle cell
alpha-actin (SMA) and Snai2. Our data demonstrated that lentiviral vector mediated CLDN1 RNA interference has great potential in
breast cancer gene therapy by inhibiting EMT and controlling
tumor cell growth.