| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 1998: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1997: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Research Abstract |
Purpose Mammalian cyclin-dependent kinase inhibitors consist of two families, the p16 family and the p21 family. These proteins are all capable of inhibiting progression of the cell cycle by binding and inhibiting GィイD21ィエD2 cyclin/cyclin-dependent kinase complexes. The p16 gene was isolated from 9p21, a chromosomal region that is a common site for loss of heterozygosity in many tumors, and found to be mutated and homozygously deleted in many types of tumors. Therefore, p16 is regarded as one of the tumor suppressor genes. On the other hand, p57 is a member of the p21 family, and the gene encoding p57 is located at 11p15.5. This region is also a common site fur loss of heterozygosity in many tumors, especially childhood tumors including Wilms' tumor, hepatoblastoma and rhabdomyosarcoma. In the current study, the author performed a mutational analysis of the p16 gene and investigated mRNA expression of the p16 and p57 genes in a variety of childhood malignant solid tumors.
Methods : Mutational analysis was done by using polymerase chain reaction-single-strand conformation polymorphism method, and for mRNA expression analyses, semi-quantitative reverse transcription polymerase chain reaction method was used.
Results : Among 111 tumors analyzed, no malignancy associated mutation was detected. However, reduced expression of the p16 gene was found in 42% (5/12) of the Wilms' tumors and 40% (4/10) of the rhabdomyosarcomas. Moreover, reduced expression of the p57 gene was also observed in 14%(2/14)of the neuroblastomas, 21% (3/14) of the hepatoblastomas, 25% (3/12) of the Wilms' tumors, and 30% (3/19) of the rhabdomyosarcomas.
Conclusions : Our data may indicate that the reduced expression of seine cyclin-dependent kinase inhibitors has a role in the pathogenesis of childhood malignant solid tumors.
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