Soung Young Hwa, Lee Jong Woo, Kim Hong Sug, Park Won Sang, Kim Su Young, Lee Jong Heun, Park Jik Young, Cho Yong Gu, Kim Chang Jae, Park Yong Gyu, Nam Suk Woo, Jeong Seong Whan, Kim Sang Ho, Lee Jung Young, Yoo Nam Jin, Lee Sug Hyung
College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Socho-gu, Seoul 137-701, Korea.
Oncogene. 2003 Sep 11;22(39):8048-52. doi: 10.1038/sj.onc.1206727.
Caspase-7 is a caspase involved in the execution phase of apoptosis. To explore the possibility that the genetic alterations of CASPASE-7 might be involved in the development of human cancers, we analysed the entire coding region and all splice sites of human CASPASE-7 gene for the detection of somatic mutations in a series of human solid cancers, including carcinomas from stomach, colon, head/neck, esophagus, urinary bladder and lung. Overall, we detected CASPASE-7 mutations in two of 98 colon carcinomas (2.0%), one of 50 esophageal carcinomas (2.0%) and one of 33 head/neck carcinomas (3.0%). We expressed the tumor-derived caspase-7 mutants in 293 T cells and found that the apoptosis was reduced compared to the wild-type caspase-7. This is the first report on the CASPASE-7 gene mutations in human malignancies, and our data suggest that the inactivating mutations of the CASPASE-7 gene might lead to the loss of its apoptotic function and contribute to the pathogenesis of some human solid cancers.
半胱天冬酶-7是一种参与细胞凋亡执行阶段的半胱天冬酶。为了探究CASPASE-7基因改变可能参与人类癌症发生发展的可能性，我们分析了人类CASPASE-7基因的整个编码区和所有剪接位点，以检测一系列人类实体癌中的体细胞突变，这些癌症包括胃癌、结肠癌、头颈癌、食管癌、膀胱癌和肺癌。总体而言，我们在98例结肠癌中的2例（2.0%）、50例食管癌中的1例（2.0%）和33例头颈癌中的1例（3.0%）检测到了CASPASE-7突变。我们在293 T细胞中表达了肿瘤来源的半胱天冬酶-7突变体，发现与野生型半胱天冬酶-7相比，细胞凋亡减少。这是关于人类恶性肿瘤中CASPASE-7基因突变的首次报道，我们的数据表明，CASPASE-7基因的失活突变可能导致其凋亡功能丧失，并有助于某些人类实体癌的发病机制。
