Research Article
Gene Therapy (2005) 12, 678–684. doi:10.1038/sj.gt.3302453 Published online 20 January 2005
Fas-ligand gene silencing in basal cell carcinoma tissue with small interfering RNA
J Ji1, M Wernli1, A Mielgo1, S A Buechner2 and P Erb1
- 1Institute for Medical Microbiology, University of Basel, Basel, Switzerland
- 2Department of Dermatology, University Hospitals Basel, Basel, Switzerland
Correspondence: Professor P Erb, Institute for Medical Microbiology, University of Basel, Petersplatz 10, CH-4003 Basel, Switzerland
Received 6 July 2004; Accepted 10 November 2004; Published online 20 January 2005.
Abstract
Basal cell carcinoma (BCC) is the most frequent cancer in the Caucasian population. Cells of BCC strongly express Fas-ligand (FasL), a member of the tumor necrosis family, which induces apoptosis in Fas receptor-expressing cells. It has been suggested that by expression of FasL, BCC cells may evade the attack of Fas-positive immune effector cells allowing the tumor to expand. Thus, downregulation of FasL should prime BCC to the assault of immune effector cells. Recently, it has been shown that RNA interference is a highly successful approach to specifically silence a gene of interest in single cells and some animal models. However, RNAi in human tissues has not been shown so far. Here, we provide evidence that small interfering RNAs (siRNAs) efficiently transfect tumor tissue ex vivo and silence the gene of interest. We demonstrate that a specific siRNA efficiently downregulates FasL not only in FasL-positive indicator cells but also in surgically excised BCC tissue at both the protein and the mRNA level. The successful transfection of tumor tissues with siRNAs now allows to test the function of the molecule under study and opens up the investigation of other target genes in the tumor.
Keywords:
basal cell carcinoma, Fas-ligand, siRNA, RNA interference, tissue transfection
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