Mutational analysis of caspase‐14 gene in common carcinomas

Aims: 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. Methods: 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. Results: 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. Conclusion: 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.

[1]  W. Park,et al.  Somatic mutations of CASP3 gene in human cancers , 2004, Human Genetics.

[2]  Jung Young Lee,et al.  Mutational analysis of the CASP6 gene in colorectal and gastric carcinomas , 2006, APMIS : acta pathologica, microbiologica, et immunologica Scandinavica.

[3]  M. Duffy,et al.  Tumor-Associated Alterations in Caspase-14 Expression in Epithelial Malignancies , 2005, Clinical Cancer Research.

[4]  S. Kumar,et al.  Mechanisms mediating caspase activation in cell death , 1999, Cell Death and Differentiation.

[5]  W. Fiers,et al.  Identification of a new caspase homologue: caspase-14 , 1998, Cell Death and Differentiation.

[6]  M. Kuechle,et al.  Processing of native caspase-14 occurs at an atypical cleavage site in normal epidermal differentiation. , 2002, Biochemical and biophysical research communications.

[7]  U. Koenig,et al.  Aberrant expression of caspase-14 in epithelial tumors. , 2005, Biochemical and biophysical research communications.

[8]  D. Nicholson,et al.  Caspase structure, proteolytic substrates, and function during apoptotic cell death , 1999, Cell Death and Differentiation.

[9]  G. Salvesen,et al.  Caspase-14 Is a Novel Developmentally Regulated Protease* , 1998, The Journal of Biological Chemistry.

[10]  H. Yamamoto,et al.  Frameshift mutations at mononucleotide repeats in caspase-5 and other target genes in endometrial and gastrointestinal cancer of the microsatellite mutator phenotype. , 1999, Cancer research.

[11]  M. Shin,et al.  Inactivating mutations of CASP10 gene in non-Hodgkin lymphomas. , 2002, Blood.

[12]  S. Schwartz,et al.  Physiological functions of caspases beyond cell death. , 2006, The American journal of pathology.

[13]  M. Shin,et al.  Alterations of Fas (Apo-1/CD95) gene in non-small cell lung cancer , 1999, Oncogene.

[14]  P. Vandenabeele,et al.  Vitamin D3 induces caspase-14 expression in psoriatic lesions and enhances caspase-14 processing in organotypic skin cultures. , 2004, The American journal of pathology.

[15]  T. Hubbard,et al.  A census of human cancer genes , 2004, Nature Reviews Cancer.

[16]  H. Edmondson,et al.  Primary carcinoma of the liver. A study of 100 cases among 48,900 necropsies , 1954, Cancer.

[17]  C. Craik,et al.  Expression and characterization of constitutively active human caspase-14. , 2006, Biochemical and biophysical research communications.

[18]  W. Park,et al.  Inactivating mutations of CASPASE-7 gene in human cancers , 2003, Oncogene.

[19]  L. Eckhart,et al.  Stratum corneum‐derived caspase‐14 is catalytically active , 2004, FEBS letters.

[20]  W. Park,et al.  Inactivating mutations of caspase-8 gene in colorectal carcinomas. , 2003, Gastroenterology.