Jang Ji-Young, Choi Yun, Jeon Yoon-Kyung, Aung Khin Chaw Yu, Kim Chul-Woo
Department of Pathology, Tumor Immunity Medical Research Center, Cancer Research Institute, Seoul National University College of Medicine, 28 Yeongeon-dong, Jongno-gu, Seoul 110-799, South Korea.
BMC Cancer. 2008 Jun 4;8:160. doi: 10.1186/1471-2407-8-160.
Adenine nucleotide translocase (ANT) is located in the inner mitochondrial membrane and catalyzes the exchange of mitochondrial ATP for cytosolic ADP. ANT has been known to be a major component of the permeability transition pore complex of mitochondria and contributes to mitochondria-mediated apoptosis. Human ANT has four isoforms (ANT1, ANT2, ANT3, and ANT4), and the expression of the ANT isoforms is variable depending on the tissue and cell type, developmental stage, and proliferation status. Among the isoforms, ANT1 is highly expressed in terminally-differentiated tissues, but expressed in low levels in proliferating cells, such as cancer cells. In particular, over-expression of ANT1 induces apoptosis in cultured tumor cells.
We applied an ANT1 gene transfer approach to induce apoptosis and to evaluate the anti-tumor effect of ANT1 in a nude mouse model.
We demonstrated that ANT1 transfection induced apoptosis of MDA-MB-231 cells, inactivated NF-kappaB activity, and increased Bax expression. ANT1-inducing apoptosis was accompanied by the disruption of mitochondrial membrane potential, cytochrome c release and the activation of caspases-9 and -3. Moreover, ANT1 transfection significantly suppressed tumor growth in vivo.
Our results suggest that ANT1 transfection may be a useful therapeutic modality for the treatment of cancer.
腺嘌呤核苷酸转位酶（ANT）位于线粒体内膜，催化线粒体ATP与胞质ADP的交换。已知ANT是线粒体通透性转换孔复合物的主要成分，并且参与线粒体介导的细胞凋亡。人ANT有四种同工型（ANT1、ANT2、ANT3和ANT4），ANT同工型的表达因组织和细胞类型、发育阶段及增殖状态而异。在这些同工型中，ANT1在终末分化组织中高表达，但在增殖细胞（如癌细胞）中低表达。特别是，ANT1的过表达可诱导培养的肿瘤细胞凋亡。
我们应用ANT1基因转导方法诱导细胞凋亡，并在裸鼠模型中评估ANT1的抗肿瘤作用。
我们证明ANT1转染可诱导MDA-MB-231细胞凋亡，使核因子-κB活性失活，并增加Bax表达。ANT1诱导的细胞凋亡伴随着线粒体膜电位的破坏、细胞色素c的释放以及半胱天冬酶-9和-3的激活。此外，ANT1转染在体内显著抑制肿瘤生长。
我们的结果表明，ANT1转染可能是一种治疗癌症的有效治疗方式。
