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KMID : 0356420110290010043
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Journal of Korean Andrology
2011 Volume.29 No. 1 p.43 ~ p.52
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Role of Clusterin and Tumor Necrosis Factor Receptors on the Apoptosis of Prostate Cancer Cells
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Joo Kwan-Joong
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Abstract
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Purpose: In prostate cancer, the anti-apoptotic mechanism of sulfated glycoprotein-2 (clusterin) against tumor necrosis factor-alpha (TNF-?) receptors and the action of type 2 TNF-? receptor (TNFR2) were investigated.
Materials and Methods: TNF-?, agonistic-TNF type 1 receptor (TNFR1) antibody, agonistic-TNF-R2 antibody and their combination were treated in PC3 cell line with or without anti-clusterin. Cytotoxicity was assessed by trypan blue dye exclusion assay. By using flowcytometric analysis, the exact amount of apoptosis and their changes were assessed.
Results: Apoptosis was significantly increased in both agonistic-TNFR1 antibody and TNF-? treated cases after blocking the activity of clusterin. The more the anti-clusterin antibody added, the more the apoptosis occurred. The increase of total apoptosis was greater in TNF-? treated cells than in agonistic-TNFR1 antibody treated ones. However, there was no increase of apoptosis in agonistic-TNFR2 antibody and TNF-? with agonistic-TNFR2 antibody treated cases, respectively.
Conclusions: Clusterin prevents TNF-? induced apoptosis by affecting TNFR1. The difference in degree of apoptosis between agonistic-TNFR1 antibody treated cells and TNF-? treated ones suggests the possibility of the action of TNFR2. It may be associated with affinity of TNF-? to the tumor cell surface.
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KEYWORD
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Prostate neoplasm, Clusterin, Tumor necrosis factor-alpha, Receptors, Tumor necrosis factor, Type II
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