CAJ | 학술논문

目的探讨尿激酶氨基末端（ATF）基因转移对肿瘤转移的抑制作用。方法构建重组ATF基因真核表达载体pcDNA3-ATF,用脂质体Lipofectin介导，将其导入其证明尿激酶（uPA）和尿激酶受体(uPAR)均有表达的人乳腺癌细胞系MCF-7。用Western blot检测转染细胞ATF基因的表达；体外观察并比较了野生型和转基因MCF-7细胞侵袭人工基底膜能力；裸鼠皮下接种癌细胞，复制自发性肿瘤转移模型，观察成瘤性和转移性。结果 uPA/uPAR在MCF-7中有较高水平的表达；转ATF基因后，可检测到ATF的明显表达，体外侵袭穿透人工基底膜的能力明显降低，体内原位成瘤性不受影响，但自主性肺转移能力有一定程度的下降。结论 ATF基因转移后，ATF的表达可能竞争性抑制内源性uPA与uPAR的结合，在一定程度上抑制癌细胞的侵袭和转移。
목적탐토뇨격매안기말단（ATF）기인전이대종류전이적억제작용。방법구건중조ATF기인진핵표체재체pcDNA3-ATF,용지질체Lipofectin개도，장기도입기증명뇨격매（uPA）화뇨격매수체(uPAR)균유표체적인유선암세포계MCF-7。용Western blot검측전염세포ATF기인적표체；체외관찰병비교료야생형화전기인MCF-7세포침습인공기저막능력；라서피하접충암세포，복제자발성종류전이모형，관찰성류성화전이성。결과 uPA/uPAR재MCF-7중유교고수평적표체；전ATF기인후，가검측도ATF적명현표체，체외침습천투인공기저막적능력명현강저，체내원위성류성불수영향，단자주성폐전이능력유일정정도적하강。결론 ATF기인전이후，ATF적표체가능경쟁성억제내원성uPA여uPAR적결합，재일정정도상억제암세포적침습화전이。
Objective　To explore the suppressive effects of urokinase amino-terminal fragment (ATF) gene on metastatic potential of human breast cancer cell line MCF-7.　Methods　A pcDNA3-ATF plasmid containing ATF cDNA under CMV promotor/enhancer control was constructed and transfected into MCF-7 cells by lipofectin. The expression of of uPA/uPAR and ATF in MCF-7 cells were analyzed by RT-PCR and Western blot. The effect of ATF expression on invasiveness in vitro, tumorigenesis and metastasis in vivo of MCF-7 cell was investigated.　Results　MCF-7 cells displayed an overexpression of uPA/uPAR. Expression of ATF was detected after ATF gene-transfection. The invasive capacity of ATF gene-transfected MCF-7 cells was decreased significantly. Although the tumorigenesis was not affected, the in vivo metastasis of ATF gene-transfected MCF-7 cells was remarkably inhibited.　Conclusion　Suppression of invasiveness and metastasis of ATF-transfected MCF-7 cells is perhaps due to a competitive inhibition of interaction with endogenous uPA/uPAR.