The superoxide scavenger TEMPOL induces urokinase receptor (uPAR) expression in human prostate cancer cells.
The superoxide scavenger TEMPOL induces urokinase receptor (uPAR) expression in human prostate cancer cells.
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DOI：
10.1186/1476-4598-5-21
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发表时间：
2006-06-06
期刊：
影响因子：
37.3
通讯作者：
Sehgal I
中科院分区：
文献类型：
--
作者：
Lejeune D;Hasanuzzaman M;Pitcock A;Francis J;Sehgal I
活性氧代谢产物在肿瘤侵袭和转移过程中对细胞行为的影响还不清楚。这些氧代谢物可以与许多调节其功能的靶点相互作用，例如参与基底膜溶解的酶、参与运动的粘附分子或参与增殖的受体。我们研究了增加超氧阴离子清除对PC-3 M人前列腺癌细胞尿激酶受体（uPAR）表达的影响。尿激酶受体（Urokinase receptor，UK）是一种与GPI连接的细胞表面分子，它介导细胞粘附、增殖和细胞周围蛋白水解等多种功能。加入超氧化物清除剂4-羟基-2，2，6，6-四甲基哌啶基氧基（TEMPOL）的PC-3 M培养物刺激的uPAR蛋白表达峰值之间的48和72小时。细胞表面uPAR的表达也增加。令人惊讶的是，uPAR转录水平仅略有增加，这种温和的增加与蛋白质增加的惊人程度不一致。这种差异表明TEMPOL对uPAR的作用是通过转录后机制发生的。TEMPOL的存在下，PC-3 M文化减少了75%的细胞内的超氧化物类型的物种测定NBT染料转换，然而，这种减少显着减少后TEMPOL去除小时内。TEMPOL处理和峰值uPAR蛋白表达之间的时间间隔表明，前列腺癌细胞中活性氧代谢物的减少启动了一个多步骤的途径，该途径需要几个小时才能在uPAR诱导中达到高潮。这些发现揭示了一个新的途径uPAR的调节涉及活性氧，如超氧阴离子。
There is little understanding of the effect that reactive oxygen metabolites have on cellular behavior during the processes of invasion and metastasis. These oxygen metabolites could interact with a number of targets modulating their function such as enzymes involved in basement membrane dissolution, adhesion molecules involved in motility or receptors involved in proliferation. We investigated the effect of increased scavenging of superoxide anions on the expression of the urokinase receptor (uPAR) in PC-3M human prostate cancer cells. Urokinase receptor is a GPI-linked cell surface molecule which mediates multiple functions including adhesion, proliferation and pericellular proteolysis. Addition of the superoxide scavenger 4-hydroxy-2,2,6,6-tetramethylpiperidinyloxy (TEMPOL) to PC-3M cultures stimulated expression of uPAR protein peaking between 48 and 72 hours. Cell surface expression of the uPAR was also increased. Surprisingly, uPAR transcript levels increased only slightly and this mild increase did not coincide with the striking degree of protein increase. This disparity indicates that the TEMPOL effect on uPAR occurs through a post-transcriptional mechanism. TEMPOL presence in PC-3M cultures reduced intracellular superoxide-type species by 75% as assayed by NBT dye conversion; however this reduction significantly diminished within hours following TEMPOL removal. The time gap between TEMPOL treatment and peak uPAR protein expression suggests that reduction of reactive oxygen metabolites in prostate cancer cells initiates a multistep pathway which requires several hours to culminate in uPAR induction. These findings reveal a novel pathway for uPAR regulation involving reactive oxygens such as superoxide anion.
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影响因子：
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