Depletion of procathepsin D gene expression by RNA interference – A potential therapeutic target for breast cancer

• DOI: 10.4161/cbt.6.7.4325
• Publication Date: 2010-07-01T18:08:11Z
• Authors: Sujata S. Ohri; Aruna Vashishta; Mary Proctor; Martin Fusek; Vaclav Vetvicka
• Keywords: 0301 basic medicine; Enzyme Precursors; NF-kappa B p50 Subunit; Breast Neoplasms; Cathepsin D; 3. Good health; Mice; 03 medical and health sciences; Cell Line, Tumor; Animals; Humans; Female; Neoplasm Invasiveness; RNA Interference; RNA, Small Interfering; cdc42 GTP-Binding Protein; Cell Proliferation

AbstractElevated level of procathepsin D (pCD), a zymogen lysosomal aspartic proteinase cathepsin D, is associated with highly invasive neoplasms that include breast cancer. Independent studies have established secreted pCD functions as growth factor acting both in an autocrine and paracrine manner. Therefore, to explore whether can be employed therapeutic target, the present study evaluates impact knockdown using RNA interference technology. Of three siRNA oligos tested, siRNA-3 exhibited 90% inhibitory effect on gene expression. Stable attenuation cancer cells MDA-MB-231 was achieved by plasmid vector-based shRNA system. Pronounced suppression expression accompanied significant reduction invasion proliferation stably transfected functional shRNA. Importantly, athymic nude mice model, downregulation significantly reduced their metastatic potential. In addition, we observed Cdc42 NF-κB2 decreased When combined, our vitro vivo experiments demonstrate targeting through RNAi technology represents potential tool for developing therapy against