Galectin-3 inhibits tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis by activating Akt in human bladder carcinoma cells
Galectin-3 inhibits tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis by activating Akt in human bladder carcinoma cells
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DOI：
10.1158/0008-5472.can-05-1197
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发表时间：
2005-09-01
期刊：
影响因子：
11.2
通讯作者：
Raz, A
中科院分区：
文献类型：
--
作者：
Oka, N;Nakahara, S;Raz, A
抗细胞凋亡分子半乳糖凝集素-3先前被证明可以调节CD 95，CD 95是细胞凋亡信号通路中肿瘤坏死因子（TNF）蛋白家族的成员。在这里，我们通过研究这个蛋白质家族的不同成员来质疑这种现象的普遍性[例如，肿瘤坏死因子相关凋亡诱导配体（TRAIL），可诱导多种癌细胞凋亡]。半乳糖凝集素-3在J82人膀胱癌细胞中的过表达使其对TRAIL诱导的凋亡具有抗性，而磷脂酰肌醇3-激酶（PI 3 K）抑制剂（wortmannin和LY-294002）阻断了半乳糖凝集素-3的保护作用。由于Akt是一个主要的下游PI 3 K的目标发挥作用的TRAIL诱导的细胞凋亡，我们质疑半乳糖凝集素-3和Akt之间的可能关系。亲本J82和对照载体转染的J82细胞（几乎检测不到半乳糖凝集素-3）表现出低水平的组成型活性Akt，导致对TRAIL的敏感性。另一方面，过表达半乳糖凝集素-3细胞的J82细胞表达高水平的组成型活性Akt，并且对TRAIL具有抗性。Akt可能通过抑制BID的裂解而阻断TRAIL诱导的J82细胞凋亡。这些结果表明，半乳糖凝集素-3涉及Akt作为一种调节分子，在保护膀胱癌细胞从TRAIL诱导的凋亡。
The antiapoptotic molecule galectin-3 was previously shown to regulate CD95, a member of the tumor necrosis factor (TNF) family of proteins in the apoptotic signaling pathway. Here, we question the generality of the phenomenon by studying a different member of this family of proteins [e.g., TNF-related apoptosis-inducing ligand (TRAIL), which induces apoptosis in a wide variety of cancer cells]. Overexpression of galectin-3 in J82 human bladder carcinoma cells rendered them resistant to TRAIL-induced apoptosis, whereas phosphatidylinositol 3-kinase (PI3K) inhibitors (wortmannin and LY-294002) blocked the galectin-3 protecting effect. Because Akt is a major downstream PI3K target reported to play a role in TRAIL-induced apoptosis, we questioned the possible relationship between galectin-3 and Akt. Parental J82 and the control vector-transfected J82 cells (barely detectable galectin-3) exhibit low level of constitutively active Akt, resulting in sensitivity to TRAIL. On the other hand, J82 cells overexpressing galectin-3 cells expressed a high level of constitutively active Akt and were resistant to TRAIL. Moreover, the blockage of TRAIL-induced apoptosis in J82 cells seemed to be mediated by Akt through the inhibition of BID cleavage. These results suggest that galectin-3 involves Akt as a modulator molecule in protecting bladder carcinoma cells from TRAIL-induced apoptosis.