Aberrant expression of caspase-14 in epithelial tumors.
Cysteine-dependent aspartate-specific proteases (caspases) are the cellular executors of apoptosis. Caspase-14 is the most divergent member of the family of mammalian caspases and displays a variety of unique characteristics. It is expressed in a limited number of tissues and has the shortest amino acid sequence within the caspase protein family. During induction of apoptosis, it is not processed, whereas terminal differentiation in skin leads to cleavage of caspase-14. Here we show that 40% of lung squamous cell carcinomas, 22% of breast cancers, and about 80% of cervical carcinomas express caspase-14. Immunohistochemistry reveals that caspase-14 is localized in areas of ongoing differentiation close to necrotic sites but is not strictly associated with the differentiation markers keratin-1/-10. Caspase-14 is neither mutated nor alternatively spliced in the tumors analyzed. Furthermore, caspase-14 is not processed into a small and large subunit, a process critical for the proteolytic activation of known effector caspases. We conclude that conditions exist in tumors leading to re-expression of this normally silent gene.
Koenig
Ulrich
U
Department of Dermatology, University of Vienna Medical School, Währinger Gürtel 18-20, A-1080 Vienna, Austria. koenigu@rockefeller.edu
Sommergruber
Wolfgang
W
Lippens
Saskia
S
D017398:Alternative Splicing; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000201:enzymology; D053456:Caspase 14; D020169:Caspases / Q000096:biosynthesis* / Q000235:genetics; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D017931:DNA Primers / Q000737:chemistry; D018076:DNA, Complementary / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D007150:Immunohistochemistry; D053556:Keratin-1; D053550:Keratin-10; D007633:Keratins / Q000096:biosynthesis; D008856:Microscopy, Fluorescence; D009154:Mutation; D009336:Necrosis; D009375:Neoplasms, Glandular and Epithelial / Q000201:enzymology*; D016133:Polymerase Chain Reaction; D012878:Skin Neoplasms / Q000201:enzymology; D014018:Tissue Distribution
D017931:DNA Primers; D018076:DNA, Complementary; C491616:KRT1 protein, human; C507493:KRT10 protein, human; D053556:Keratin-1; D053550:Keratin-10; D007633:Keratins; C506446:CASP14 protein, human; D053456:Caspase 14; D020169:Caspases