| Co-Investigator(Kenkyū-buntansha) |
NAGAI Hirokazu SCHOOL OF MEDICINE, Nagoya University, MEDICAL STAFF, 医学部, 医員
MURATE Takashi SCHOOL OF MEDICINE, Nagoya University, PROFESSOR, 医学部, 教授 (30239537)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2000: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1999: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Research Abstract |
We have identified frequent loss of heterozygosity (LOH) at 1q, 3p, 6p, and 6q in B-cell non-Hodgkin lymphomaby allelotype studies. We have conducted fine deletion mapping on 6p and identified two common deleted regions, one is between D6S1721 and D6S260 (at 6p23-24), and the other between D6S265 and D6S291 (at 6p21). Next we started a search for a novel tumor suppressor gene on 1q. PROX1, a homologue of Drosophilla homeobox gene, is located on chromosome 1q32, which is a common chromosomal deleted lesion in malignant lymphoma that we have identified. Although PROX1 mRNA is ubiquitously expressed in normal hematolymphoid systems, it was not expressed in several hematolymphoid cell lines. PROX1 expression in Raji cell was not detected by RT-PCR method, but it was restored after 5-AzaC treatment. Nucleotide sequence analysis after bisulfite modification revealed that PROX1 expression in hematolymphoid cell lines and normal peripheral blood mononuclear cells was correlated very well with hypermethylation in intron 1 of PROX1 gene. Mutational analyses of PROX1 gene have revealed 6 missence and/or nonsense mutations in 5 cell lines (BALL1, HEL, THP6, RPMI8402 and Jurkat). These results indicated that PROX1 is inactivated in several hematolymphoid neoplasms, mainly by DNA methylation. These results strongly suggested that PROX1 is a novel candidate for tumor suppressor gene that is related to hematolymhoid neoplasms. Since PROX1 function as a tumor suppressor is still uncertain, we are now evaluating PROX1 functions on cellular growth or transformation.
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