Increased manganese superoxide dismutase (SOD-2) is part of the mechanism for prostate tumor suppression by Mac25/insulin-like growth factor binding-protein-related protein-1
Increased manganese superoxide dismutase (SOD-2) is part of the mechanism for prostate tumor suppression by Mac25/insulin-like growth factor binding-protein-related protein-1
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DOI：
10.1038/sj.onc.1206210
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发表时间：
2003-02-20
期刊：
影响因子：
8
通讯作者：
Oberley, TD
中科院分区：
文献类型：
--
作者：
Plymate, SR;Haugk, KH;Oberley, TD
mac25/胰岛素样生长因子结合蛋白相关蛋白-1 （IGFBP-rP1）在人乳腺和前列腺上皮细胞系中的表达增加，抑制肿瘤生长。CDNA表达阵列分析显示，与M12对照细胞相比，mac25/ igfbp - rp1转染的M12人前列腺癌细胞株中锰超氧化物歧化酶（SOD-2）的表达增加。SOD-2被认为是一种肿瘤抑制因子。在稳定转染mac25/IGFBP-rP1的LNCaP细胞中，SOD-2也增加，而在转染mac25/IGFBP-rP1的PC-3细胞中，SOD-2没有增加。与对照组相比，Mac25 LNCaP细胞在裸鼠中的肿瘤生长明显下降，而Mac25 PC-3细胞的肿瘤生长与对照组相比没有差异。M12和LNCaP转染的mac25/ IGFBP-rP1细胞中磷酸化的Erk和Akt升高，PC-3 mac25细胞中磷酸化的Erk和Akt升高。与M12对照相比，PI-3激酶的抑制导致M12-mac25细胞活力明显下降。用H2O2处理的细胞导致磷酸化erk增加。在M12细胞中转染SOD-2可显著降低肿瘤生长、细胞凋亡、细胞周期G1延迟以及衰老相关β -半乳糖苷酶的表达。这些结果表明，mac25/IGFBP-rP1的衰老相关肿瘤抑制作用的下游介质之一是SOD-2。
Increased expression of mac25/insulin-like growth factor binding-protein related protein-1 (IGFBP-rP1) in human breast and prostate epithelial cell lines results in the suppression of tumor growth. CDNA expression array analysis revealed increased manganese superoxide dismutase (SOD-2) expression in the mac25/IGFBP-rP1-transfected M12 human prostate cancer cell line compared to M12 control cells. SOD-2 has been postulated to be a tumor suppressor. SOD-2 was also increased in LNCaP cells stably transfected with mac25/IGFBP-rP1, but not in mac25/IGFBP-rP1-transfected PC-3 cells. Mac25 LNCaP cells had a marked decrease in tumor growth in nude mice compared to controls, but there was no difference in tumor growth in mac25 PC-3 cells compared to control. Phosphorylated Erk and Akt were increased in the M12 and LNCaP transfected mac25/ IGFBP-rP1 cells but not PC-3 mac25. Inhibition of PI-3 kinase results in a marked decrease in viability of the M12-mac25 cells compared to M12 controls. Cells treated with H2O2 result, in an increase in phospho-ERK. Transfection of SOD-2 in M12 cells markedly decreased tumor growth, apoptosis, G1 delay in the cell cycle, and expression of senescence associated beta-galactosidase. These results suggest that one of the downstream mediators of the senescence-associated tumor suppression effect of mac25/IGFBP-rP1 is SOD-2.