| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Research Abstract |
We newly established human tongue keratinocytes (HTK) cell lines derived from tongue mucosa with retroviral vectors expressing mutant CDK4, cyclinD1, hTERT and dominant negative form of p53. Additional transduction of oncogenic Hras or EGFR together with c-Myc into the HTK-K4DT-DNp53 showed subcutaneous tumor formation in nude mice only around 2 weeks. To determine the frequency of oral cancer initiating cells within these cells, a limiting dilution assay was performed. Orthotopic transplantation of HTK-K4DT-DNp53-Hras-cMyc resulted inlocal growth of tumors in all the mice tested and some of them yielded regional metstastases in 2-3 weeks.We have established an in vitro model for OSCCs with normal human tongue keratinocytes (HTKs) focusing on sequential transduction of defined genetic elements and succeeded in the creation of highly potent cancer initiating cells by introduction of c-MYC and oncogenic Hras on a background of the blockade of the pRB and p53 pathways .
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