Integrin-linked kinase is involved in lactoferrin-induced anchorage-independent cell growth and survival in PC12 cells.
Integrin-linked kinase is involved in lactoferrin-induced anchorage-independent cell growth and survival in PC12 cells.
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DOI：
10.1016/j.lfs.2009.01.025
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发表时间：
2009-04
期刊：
影响因子：
6.1
通讯作者：
T. Ishii;T. Uto;Kaori Mori;Ryu Fujikawa
中科院分区：
文献类型：
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作者：
T. Ishii;T. Uto;Kaori Mori;Ryu Fujikawa
目的牛乳铁蛋白（bLf）在PC 12细胞中引起非贴壁依赖性细胞生长。本研究探讨了bLf诱导PC 12细胞贴壁生长和存活的机制。(570关键发现整合素连接激酶（ILK）在整合素和生长因子信号通路中起重要作用。用ILK的显性负性激酶缺陷突变体（DN-ILK）稳定转染PC 12细胞抑制bLf诱导的锚定非依赖性细胞生长。ILK在亲本细胞中的活性在加入bLf后被瞬时激活，而bLf诱导的ILK激活在DN-ILK转染的细胞中被阻断。bLf还激活p38丝裂原活化蛋白激酶（MAPK）;然而，稳定的DN-ILK转染抑制了p38 MAPK的激活。此外，在bLf悬浮细胞的细胞活力强烈下降后，SB 203580，p38 MAPK的抑制剂处理。
AIMSBovine lactoferrin (bLf) causes anchorage-independent cell growth in PC12 cells. The present study investigated the mechanisms involved in bLf-induced anchorage-independent cell growth and survival in PC12 cells.MAIN METHODSThe number of adherent cells and suspended cells was estimated separately by using a methyl thiazol tetrazolium (MTT) assay, and the sum of both optical density (O.D.) (570 nm) values was used as a measure of the total number of cells.KEY FINDINGSIntegrin-linked kinase (ILK) plays an important role in integrin and growth factor signaling pathways. Stable transfection of PC12 cells with a dominant negative kinase-deficient mutant of ILK (DN-ILK) inhibited bLf-induced anchorage-independent cell growth. The ILK activity in the parental cells was transiently activated after addition of bLf, whereas bLf-induced activation of ILK was blocked in DN-ILK-transfected cells. bLf also activated p38 mitogen-activated protein kinase (MAPK); however, the p38 MAPK activation was inhibited by stable DN-ILK transfection. Moreover, cell viability in the suspended cells by bLf strongly decreased after treatment with SB203580, an inhibitor of p38 MAPK.SIGNIFICANCEThese results suggest that ILK is involved in bLf-induced anchorage-independent cell growth and viability via activation of p38 MAPK.