| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2004: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Research Abstract |
In a previous study, we showed that expression of a transcription factor-high mobility group protein (HMGIC/HMGA2), which plays a critical role in differentiation and growth of un-differentiated mesenchymal cells during development, is frequently observed in oral carcinomas and associates with 5-year survival rate of patients suffered from the disease. Understanding a role of HMGIC expression should expand knowledge of a molecular mechanism(s) of cancer progression. In this end, we developed a novel high-throughput analysis, named sChIP, to unveil HMGA2 target genes. We identified approx. 100 genes, and focused on 5 different genes, which are expected to be involved in the progression of oral carcinomas. RT-PCR showed that expression of these 5 genes were negligible in differentiated HaCaT keratinocytes but upregulated in undifferentiated HaCaT cells. In addition, oral carcinoma cells without HMGIC expression (KOSC3, Ho1u1) did not express these 5 genes in contrast to the expression in carcinoma cells expressing HMGIC gene (HOC313, TSU). To understand the transcriptional activity of HMGIC, we are currently investigating it by a reporter assay using luciferase system. Expression of HMGIC target genes in keratinocytes isolated from Hmgic-null mice is also under investigation. We will develop carcinoma cell lines which are specifically knock-downed HMGA2 gene by RNAi, and analyze a direct role of HMGIC and the target genes on tumorgenisity, and invasiveness, metastatic potential and phenotypic alterations of carcinoma cells.
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