ABSTRACT 376(7-2)
Crk癌化細胞のMMP-2の活性化はc-Rasを必要とする: 劉 恩波1, タン エイエイ2, 吉川史隆1, 濱口道成2 (名大1 産婦、2病態研 分子病態)
MMP-2 activition in crk-transfected fibroblast is c-Ras dependent : Enbo LIU1, Aye Aye THANT2, Fumitaka KIKKAWA1, Michinari HAMAGUCHI2 ( 1Dept. Obstet Gynecol, 2Res. Inst. Dis. Mech. &Cont., Nagoya Univ. Sch. Med.)
To study the signaling pathway critical for tumor invasion, we examined the effects of dominant negative ras ( S17N ras ) expression on the production and activition of MMP-2 in crk-transfected 3Y1 cells. MMP-2 is known to be a zinc-containing endo-proteinase that is responsible for proteolytic degradation of specific extracellular matrix ( ECM ) components, and plays a key role in cancer invasion and metastasis. v-Crk overexpressing 3Y1 cells were stably transfected with a dominant negative ras ( S17Nras ) under the control of conditionally inducible MMTV promoter. In crk-transfected 3Y1 cells, expression of S17N Ras did not suppress either Crk expression or tyrosine phosphorylation of cellular proteins, but strongly inhibited the augmented secretion and proteolytic activition of MMP-2. Thus these results strongly suggest that c-Ras signaling is required for the activition of MMP-2 in crk-transfected 3Y1 cells.