Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University, Wonju 220-710, Korea.
BMB Rep. 2012 Sep;45(9):526-31. doi: 10.5483/bmbrep.2012.45.9.104.
Many malignant tumors become resistant to tumor necrosis factor-alpha (TNF-α)-induced cell death during carcinogenesis. In the present study, we examined whether parkin acts as a tumor suppressor in HeLa cells, a human cervical cancer cell line resistant to TNF-α-induced cell death. TNF-α-treatment alone did not affect HeLa cell viability. However, expression of parkin restored TNF-α-induced apoptosis in HeLa cells. Increased cell death was due to the activation of the apoptotic pathway. Expression of parkin in TNF-α-treated HeLa cells stimulated cleavage of the pro-apoptotic proteins caspase-8, -9, -3, -7 and poly ADP ribose polymerase (PARP). In addition, parkin expression resulted in decreased expression of the caspase inhibitory protein, survivin. These results suggest that parkin acts as a tumor suppressor in human cervical cancer cells by modulating survivin expression and caspase activity. We propose that this pathway is a novel molecular mechanism by which parkin functions as a tumor suppressor.
在癌变过程中，许多恶性肿瘤对肿瘤坏死因子-α（TNF-α）诱导的细胞死亡产生抗性。在本研究中，我们研究了 parkin 是否作为人宫颈癌细胞系 HeLa 中的肿瘤抑制因子发挥作用，该细胞系对 TNF-α诱导的细胞死亡具有抗性。TNF-α 单独处理不会影响 HeLa 细胞活力。然而，parkin 的表达恢复了 TNF-α 诱导的 HeLa 细胞凋亡。细胞死亡的增加是由于凋亡途径的激活。在 TNF-α 处理的 HeLa 细胞中表达 parkin 可刺激促凋亡蛋白 caspase-8、-9、-3、-7 和多聚 ADP 核糖聚合酶（PARP）的切割。此外，parkin 的表达导致 caspase 抑制蛋白 survivin 的表达减少。这些结果表明，parkin 通过调节 survivin 表达和 caspase 活性作为人类宫颈癌中的肿瘤抑制因子发挥作用。我们提出，该途径是 parkin 作为肿瘤抑制因子发挥作用的新的分子机制。
