| Budget Amount *help |
¥40,500,000 (Direct Cost: ¥40,500,000)
Fiscal Year 1998: ¥8,100,000 (Direct Cost: ¥8,100,000)
Fiscal Year 1997: ¥13,200,000 (Direct Cost: ¥13,200,000)
Fiscal Year 1996: ¥19,200,000 (Direct Cost: ¥19,200,000)
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| Research Abstract |
MRP-1/CD9 belongs to the transmembrane 4 superfamily (TM4SF), which includes at least 19 members that are expressed on various tissues.Apart from MRP-1/CD9, two other members of the TM4 SF, KAI1/CD82 and ME491/CD63 are noted for their involvement in tumor progression and metastasis.However, the ME491/CD63 mRNA levels in almost all of the lung cancers, breast cancers and pancreas cancers were well preserved and no reductions were detected.In contrast, ME491/CD63 is associated with other TM4SF members, CD81 and MRP-1/CD9.In addition, CD81 and KAI1/CD82 formed multimolecular membrane complexes by associating with each other and with integrin alpha3 alpha4 alpha6 and beta6.This is true of MRP-1/CD9.Therefore, TM4SF members may act in large multicomponent complexes, and serve as receptor-associated ion channels or may act to transduce of signals across the plasma membrane and to regulate cell activation, development, proliferation, and motility.Moreover, we can predict the prognosis of pati
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ents with lung cancers, breast cancers or pancreas cancers more precisely by evaluating the expression of both MRP-1/CD9 and KAI1/CD82.Considering the progression of malignant tumors, the reduction in KAI1/CD82 might precede the reduction in MRP-1/CD9.The tumor suppressor genes, p53 or RB had been mutated or deleted during the early stage of these tumors and thus the KAI1/CD82 gene might be in decline.During the last stage, the levels of MRP-1/CD9 might be diminishing due to methylation of the promoter and therefore the normal functions of MRP-1/CD9 could be lost.Thus, the malignant cells could finally acquire metastatic potential.Therefore, we investigated the possibility of preventing metastasis of BL6 by expression of MRP-1/CD9 through gene transfer.A replication-deficient adenovirus vector was used for the in vivo transfer of MRP-1/CD9 cDNA.Intravenous injection of an adenovirus vector (rAd-MRP-1/CD9) expressing MRP-1/CD9 resulted in a 85% reduction in the number of pulmonary metastases of mice and the median survival time of mice treated with rAd-MRP-1/CD9 was significantly longer than those treated with the rAd-betagal vector. Less
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