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RNAi as a Tool for Mammalian Gene Analysis: Applications of siRNAs

of the same target gene should have therapeutic value.

* Filleur et al (4) showed that the antiangiogenic molecule thrombospondin-1 (TSP-1) could reduce vascularization and delay tumor onset. Over time, tumor cells producing active TSP1 began to form exponentially growing tumors. These tumors were composed of cells secreting unusually high amounts of the angiogenic stimulator, vascular endothelial growth factor (VEGF), which were sufficient to overcome the inhibitory TSP1. Treating tumor cells with a combination of TSP1 and a VEGF-specific siRNA caused a striking reduction in cell proliferation. This result suggested that using a combination of TSP1 and an anti-VEGF compound would slow or eliminate tumor growth.

* Based on the observation that fatty acid synthase (FASE) is over-expressed in human epithelial cells, De Schrijver et al (5) considered the gene to be an interesting target for antineoplastic therapy. The researchers used siRNAs to reduce the expression of FASE in lymph node carcinoma of the prostate (LNCaP) cells. The FASE siRNAs caused several phenotypes in the LNCaP cells, including induction of apoptosis. Interestingly, the FASE siRNAs had no effect on the growth rate or viability of nonmalignant cultured skin fibroblasts. These data point out the potential of cancer drugs that selectively inhibit FASE.

* Cyclin E is overexpressed in a number of tumor cells. To determine the potential value of the gene
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