Yoo Nam Jin, Soung Young Hwa, Lee Sung Hak, Jeong Eun Goo, Lee Sug Hyung
Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Pathology. 2007 Jun;39(3):330-3. doi: 10.1080/00313020701329815.
Whereas most caspases play roles in apoptosis and/or inflammation, caspase-14 plays a main role in epithelial differentiation. In cancers, expression of caspase-14 is frequently altered and is associated with some clinicopathological characteristics, suggesting caspase-14 might contribute to the pathogenesis of cancers. As a potential mechanism of caspase-14 alterations in cancers, we explored the possibility that mutation of caspase-14 gene is a characteristic of human cancers.
We analysed the entire coding region and all splice sites of human caspase-14 gene for the detection of somatic mutations in a series of 345 cancers, including 105 colorectal, 60 gastric, 60 hepatocellular, 60 breast and 60 lung carcinomas, by a single-strand conformation polymorphism (SSCP) assay.
Overall, we detected two somatic mutations of caspase-14 gene, which consisted of one missense mutation (S32Y) and one silent mutation (T234T). The caspase-14 mutations were detected in two of 105 colorectal carcinomas (1.9%), but not in other carcinomas.
These data indicate that caspase-14 gene is rarely mutated in colorectal carcinomas, but not mutated in gastric, lung, breast and hepatocellular carcinomas. The data also suggest that the caspase-14 mutation may not be a direct target of inactivation in tumorigenesis of common carcinomas.
大多数半胱天冬酶在细胞凋亡和/或炎症中发挥作用,而半胱天冬酶-14在上皮分化中起主要作用。在癌症中,半胱天冬酶-14的表达经常发生改变,并与一些临床病理特征相关,这表明半胱天冬酶-14可能参与癌症的发病机制。作为癌症中半胱天冬酶-14改变的一种潜在机制,我们探讨了半胱天冬酶-14基因突变是人类癌症特征的可能性。
我们通过单链构象多态性(SSCP)分析,检测了345例癌症(包括105例结直肠癌、60例胃癌、60例肝细胞癌、60例乳腺癌和60例肺癌)中人类半胱天冬酶-14基因的整个编码区和所有剪接位点,以检测体细胞突变。
总体而言,我们检测到半胱天冬酶-14基因的两个体细胞突变,其中包括一个错义突变(S32Y)和一个沉默突变(T234T)。在105例结直肠癌中有2例(1.9%)检测到半胱天冬酶-14突变,但在其他癌症中未检测到。
这些数据表明,半胱天冬酶-14基因在结直肠癌中很少发生突变,但在胃癌、肺癌、乳腺癌和肝细胞癌中未发生突变。这些数据还表明,半胱天冬酶-14突变可能不是常见癌症肿瘤发生过程中失活的直接靶点。