| Budget Amount *help |
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1995: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1994: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Research Abstract |
The chromosome translocations ocurring at chromosome 11 band q23 (11q23) are identified as a nonrandam cytogenetic event in various kinds of leukemias and lymphomas. We cloned the breakpoints of t (11 ; 14) (q23 ; q32) in B-cell lymphoma and t (11 ; 19) (q123 ; p13) in an infantile leukemia and identified the target genes on 11q23, RCK and MLL,respectively. The RCK gene product is a member of DEAD box protein/RNA helicase family. Expression of the RCK gene was studied by Northern and Western blot analyzes. By Northern blot analysis, a 7.5 kb transcript of the RCK gene was shown to be expressed ubiquitously in human and mouse tissues. Polyclonal antibodies against RCK gene product were raised and RCK gene expression pattern was examined in human and mouse tissues. Two different polyclonal antirck antibodies detected a specific 54-kilodalton product named rck/p54 in the majority of human and mouse tissues tested by Western blot analysis. However, rck/p54 was shown to be very low in the human brain and was not detectable in lumbar muscle and lung tissues. Interestingly, malignant transformed human cells arising from the tissues with low or no expression of rck/p54, such as neuroblastoma, glioblastoma, rhabdomyosarcoma and lung cancer cell lines produced a moderate amount of rck/p54 protein, suggesting that rck/p54 plays a role on tumorigenesis.
On the other hand, the MLL of 15 kb transcript was shown to be homologous to the tritrax gene of Drosophila, which is a transcription factor, and involved in vast major 11q23 translocations of leukemias. We also demonstrated that the chimeric MLL transcripts are found in all cases and the breakpoints are localized to the 3' side of the zink finger region.
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