| Budget Amount *help |
¥3,800,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥300,000)
Fiscal Year 2007: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2006: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2005: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Research Abstract |
Survivin, a new member of the inhibitor of apoptosis protein (IAP) family, has been reported to be expressed in cancers. We identified a novel splice variant of survivin, designated as survivin-3B (accession No.AB154416). It comprises 5 exons including novel exon 3B derived from a 165-bp long portion of intron 3. It contains a single bacurovirus IAP repeat (BIR). Expression of survivin-3B was detected in human colon and gastric adenocarcinoma cell lines as well as samples from patients with myelodysplastic syndrome and acute leukemia. However, biological role of survivin-3B remains unclear. We performed experiments to examine its function. Overexpression of survivin-3B in leukemia and colon cancer cells reduced cell death after etoposide and cispla tin treatment, suggesting its anti-apoptotic property. Four types of short h airpin RNAs (shRNAs) (#1#4) were designed, targeting both survivin itself and survivin-3B. The lentivirus-mediated shRNA delivery strongly suppressed H L-60 leukemia growth. These data indicate that survivin-3B possesses anti-apoptotic function. Both survivin-3B and survivin-directed RNA interference is a potent suppressor of leukemia growth.
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