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Research Paper
Depletion of Procathepsin D Gene Expression by RNA Interference – A Potential Therapeutic Target for Breast Cancer
Sujata S. Ohri, Aruna Vashishta, Mary Proctor, Martin Fusek and Vaclav Vetvicka
volume 6 | issue 7
July 2007Pages: 1081 - 1087
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Elevated level of procathepsin D (pCD), a zymogen of lysosomal aspartic proteinase cathepsin D, is associated with highly invasive neoplasms that include breast cancer. Independent studies have established that secreted pCD functions as a growth factor acting both in an autocrine and paracrine manner. Therefore, to explore whether pCD can be employed as a therapeutic target, the present study evaluates the impact of pCD knockdown using RNA interference technology. Of the three siRNA oligos tested, siRNA-3 exhibited a 90% inhibitory effect on pCD gene expression. Stable attenuation of pCD in breast cancer cells MDA-MB-231 was achieved by using a plasmid vector-based shRNA system. Pronounced suppression of pCD expression was accompanied by a significant reduction in invasion and proliferation of MDA-MB-231 cells stably transfected with functional shRNA. Importantly, in the athymic nude mice model, downregulation of pCD in breast cancer cells significantly reduced their metastatic potential. In addition, we observed a reduction in Cdc42 and NF-κB2 expression in MDA-MB-231 cells with decreased pCD expression. When combined, our in vitro and in vivo experiments demonstrate that targeting pCD through RNAi technology represents a potential therapeutic tool for developing a therapy against breast cancer.
Authors
Sujata S. Ohri
University of Louisville, Louisville, Kentucky USA
Aruna Vashishta
University of Louisville, Louisville, Kentucky USA
Mary Proctor
University of Louisville, Louisville, Kentucky USA
Martin Fusek
Czech Academy of Science, Prague, Czech Republic
Vaclav Vetvicka
University of Louisville, Louisville, Kentucky USA
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDFIf the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.