Department of Biochemistry and Molecular Biology, Shanghai Jiaotong University School of Medicine, Shanghai, PR China.
Mol Med Rep. 2012 Jul;6(1):121-4. doi: 10.3892/mmr.2012.860. Epub 2012 Apr 6.
The human WWOX gene, known as WW domain-containing oxidoreductase, is located on 16q23.3-24.1, a chromosome region that spans the common fragile site, FRA16D. Abnormal transcripts or even loss of expression are frequently found in a number of cancer cell types, including breast, ovarian, prostate and lung cancer cells. It has therefore been proposed that the WWOX gene encodes a candidate tumor suppressor, possibly a pro-apoptotic protein. However, the mechanism behind this is not entirely clear. In the present study, we examined the pro-apoptotic action of WWOX using transient expression in A549 cells. We observed that the ectopic expression of WWOX caused apoptosis in A549 cells. We further observed procaspase-3 and procaspase-9 activation and the release of cytochrome C from the mitochondria in A549 cells transfected with pcDNA3.0-WWOX. These data indicate that WWOX induces apoptosis in A549 cells via the mitochondrial pathway.
人类 WW0X 基因，又称 WW 结构域氧化还原酶，位于 16q23.3-24.1 染色体区域，跨越常见的脆性部位 FRA16D。在许多癌细胞类型中，包括乳腺癌、卵巢癌、前列腺癌和肺癌细胞中，经常发现异常转录本甚至表达缺失。因此，有人提出 WW0X 基因编码候选肿瘤抑制因子，可能是一种促凋亡蛋白。然而，其背后的机制尚不完全清楚。在本研究中，我们通过瞬时转染 A549 细胞来研究 WW0X 的促凋亡作用。我们观察到，外源性表达 WW0X 导致 A549 细胞凋亡。我们进一步观察到转染 pcDNA3.0-WWOX 的 A549 细胞中 caspase-3 和 caspase-9 的激活以及线粒体中细胞色素 C 的释放。这些数据表明，WW0X 通过线粒体途径诱导 A549 细胞凋亡。
