| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Outline of Final Research Achievements |
Transposon-based insertional mutagenesis provides a method for an unbiased forward genetic screen for cancer genes in mice. Using this system, we identified an RNA-binding protein, La-related protein 4b (LARP4B), as a candidate cancer gene for GBM. The patterns of transposon insertions predict that Larp4b has a tumor suppressor function. LARP4B expression was consistently decreased in human GBM cell lines. Moreover, heterozygous deletion of LARP4B was detected in nearly 80% of GBMs in TCGA database. LARP4B loss resulted in low expression levels, and was associated with poor patient survival. LARP4B transduction into GBM cell lines strongly inhibited proliferation. Loss of function of Larp4b in mouse primary astrocytes promoted proliferation and led to tumor formation in combination with deficiency of p53 and Nf1. Taken together, these data provide strong evidence that LARP4B serves as a tumor suppressor gene in GBM.
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