|Budget Amount *help
¥6,400,000 (Direct Cost : ¥6,400,000)
Fiscal Year 1995 : ¥1,800,000 (Direct Cost : ¥1,800,000)
Fiscal Year 1994 : ¥4,600,000 (Direct Cost : ¥4,600,000)
In our previous studies we showed that motility related protein-1 (MRP-1) is a glycoprotein recognized by monoclonal antibody (MAb) M31-15, and that the sequence of MRP-1 is identical to that of CD9, a white cell differentiation antigen. Transfection of MRP-1/CD9 cDNA into cultured non-hematopoietic cells suppresses cell motility. The extent of suppression is directly related to the level of MRP-1/CD9 expression. In addition, the metastatic potential of MRP-1/CD9-transfected melanoma cells BL6 is lower than that of control BL6 cells. To determine whether these experimental results are of relevance with respect to actual human tumors, we investigated MRP-1/CD9 expression in 143 invasive ductal carcinomas of the breast. Of 97 patients with MRP-1/CD9-positive tumors, only 36 (37.1%) had lymph node involvement. By contrast, 21/39 (53.8%) patients whose tumors had reduced MRP-1/CD9 immunoreactivity, and 5/7 patients whose primary carcinomas were not stained by the anti-MRP-1/CD9 MAb had lym
ph node metastases. The comparison of protein expression by 62 primary tumors and their respective metastatic lymph nodes revealed that in almost 50% of the cases the latter had lower MRP-1/CD9 levels than the former. Moreover, reverse transcriptase polymerase chain reaction (RT-PCR)-based analysis disclosed that MRP-1/CD9 gene expression in the metastatic lymph nodes of 17/32 patients was strikingly lower than in the primary invasive ductal carcinomas. Gene overexpression was not observed in any of the samples studied. Our data suggest that low MRP-1/CD9 expression may be associated with the metastatic potential of certain human tumors. In consideration of these findings, we have now applied RT-PCR to determine MRP-1/CD9 gene expression in lung cancer. We analyzed tumor tissues of 109 patients ; 49 tumors were stage I,15, stage II and 45, stage III.We found that 67 patients had MRP-1/CD9 -positive tumors, and that gene expression was reduced in the tumors of the remaining 42 individuals. The overall rate of survival was strikingly higher among patients with positive tumors than in those whose tumors had reduced gene expression (62.3% vs.34.9% ; p<0.001). This also pertained to patients with adenocarcinomas of the lung (55.4% vs.26.0% ; p<0.001). Multivariate analysis with the Cox regression model indicated that MRP-1/CD9 positivity correlated better with overall survival rate than other variables, except lymph node status. Our data suggest that low MRP-1/CD9 expression by tumors of the lung may be associated with poor prognosis. It is conceivable that testing for MRP-1/CD9 may identify node-negative lung cancer patients and patients with adenocarcinomas who are at high risk for early disease recurrence. On the other hand, sequence analysis with lung cancer revealed that MRP-1/CD9 have the hot spots at codon 143 and 163, both of which change from A to G.The former aminoacid changes are from LYS to ARG,and the latter from ASN to ASP.
そこで,109例のIIIb期までの術後肺癌症例を用いて,retrospective studyを行い,RT-PCRを用いてmRNAのレベルでMRP-1/CD9を評価した.その結果,MRP-1/CD9減弱群は現時点での全生存率が34.9%であるのに対して,保持群では62.3%と高値を示した.MRP-1/CD9減弱群は有意に予後不良であった(p<0.001).このことは特に肺腺癌症例で著明で,減弱群では全生存率が26.0%であるのに対して,保持群では55.4%であり,MRP-1/CD9減弱群は有意に予後不良であった(p<0.001)・Coxの比例ハザードモデルで解析を行った結果,MRP-1/CD9の減弱は,N因子に次いで有意な独立した予後不良因子であることが判明した.また,同時に行ったDNAシークエンスで143番目及び163番目のコドンがAからGに置換されることがあるが判明した.アミノ酸配列ではそれぞれLYSからARG,ASNからASPであった.これらの意味については現在検討中である. Less