Coordinated expression of matrilysin during TPA-induced apoptosis of LNCaP cells: two parallel processes affected by TPA.

Coordinated expression of matrilysin during TPA-induced apoptosis of LNCaP cells: two parallel processes affected by TPA.
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TPA 诱导的 LNCaP 细胞凋亡过程中基质溶解素的协调表达:受 TPA 影响的两个平行过程。

DOI:
10.1016/s0304-3835(96)04552-1
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发表时间:
1997
期刊:
影响因子:
9.7
通讯作者:
Bowden,GT
Bowden,GT
中科院分区:
医学1区
文献类型:
--
作者:
Sundareshan,P;Koster,JJ;Nagle,RB;Bowden,GT

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基质金属蛋白酶(MMPs)被生长因子和12-O-十四酰佛波醇-13-乙酸酯(TPA)上调。TPA(10 NM)可诱导高密度无血清培养的LNCaP细胞发生凋亡,并使基质溶素的表达水平升高。TPA诱导的DNA梯状条带仅在10h出现,TPA诱导的细胞凋亡在12h出现,提示基质溶素在细胞凋亡中具有一定的作用。然而,当使用基质金属蛋白酶抑制剂BB-2516时(25μM,基质溶素的IC50为20 nM),BB-2516对TPA诱导的LNCaP细胞的凋亡没有影响(P=0.2072)。这一观察结果表明,包括基质溶素在内的MMPs在TPA诱导的LNCaP细胞凋亡中不起主要作用。我们认为,TPA诱导的细胞凋亡和含有TPA反应元件(TPA-Response Element,TRE)的Matrilysin基因的调控是独立的、平行的过程。
Matrix metalloproteinases (MMPs) are upregulated by growth factors and 12-O-tetradecanoyl-phorbol-13-acetate (TPA). TPA (10 nM) induced apoptosis in LNCaP cells grown in serum-free medium at high seeding density, and increased mRNA and secreted protein levels for the MMP matrilysin. While the TPA-augmented increase in matrilysin mRNA was seen at 4 h, secreted matrilysin protein levels at 8 h, TPA-induced DNA ladder formation was seen only at 10 h and the TPA-induced apoptosis was detected at 12 h. The sequence of events suggested a functional role for matrilysin in apoptosis. However, when the MMP inhibitor BB-2516 was used (25 μM, with IC50of 20 nM for matrilysin), there was no effect of BB-2516 on TPA-induced apoptosis in LNCaP cells (P = 0.2072). This observation indicates that MMPs including matrilysin do not play a primary role in TPA-induced apoptosis in LNCaP cells. We conclude that the TPA-induced apoptosis and the regulation of matrilysin (a TPA-response element (TRE)-containing gene), are independent and parallel processes.
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DOI: 10.1210/endo-122-2-552
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