Loss of caspase-1 gene expression in human gastric carcinomas and cell lines.
The caspases are a family of aspartic acid-specific proteases that fulfill varied and often critical roles in mammalian apoptosis or in the proteolytic activation of cytokines. Caspase-1 (interleukin-1beta-converting enzyme) is a member of the cysteine protease family, which cleaves target proteins following aspartic acid residues. We investigated caspase-1 expression in stomach cancer, tissues and cell lines. Of 301 consecutive gastric carcinomas, 58 cases (19.3%) showed the expressional loss of caspase-1. Loss of caspase-1 expression was significantly associated with pTNM stage (p=0.03), lymph node metastasis (p=0.01) and patient survival (p<0.01). Caspase-1 expression was also significantly correlated in an inverse manner with p53 expression (p<0.01). Among the 11 gastric cancer cell lines examined, three cell lines showed loss of expression at the protein and mRNA levels. On treatment with 5-aza-2'-deoxycytidine (5-aza-C), and/or trichostatin A (TSA), all three cell lines re-expressed caspase-1 mRNA. The above findings suggest that epigenetic events such as DNA methylation and histone deacetylation play important roles in the regulation of caspase-1, and that loss of caspase-1 expression is associated with poor survival in gastric carcinoma.
Jee
Chang Do
CD
Cancer Research Institute, Seoul National University College of Medicine, Seoul 110-799, Korea.
Lee
Hye Seung
HS
Bae
Soo In
SI
Yang
Han Kwang
HK
Lee
You Mie
YM
Rho
Min Suk
MS
Kim
Woo Ho
WH
D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology; D020170:Caspase 1 / Q000096:biosynthesis* / Q000235:genetics*; D019175:DNA Methylation; D000077209:Decitabine; D005260:Female; D020869:Gene Expression Profiling; D006657:Histones / Q000378:metabolism; D006801:Humans; D008207:Lymphatic Metastasis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology; D016019:Survival Analysis; D014407:Tumor Cells, Cultured
D000964:Antimetabolites, Antineoplastic; D006657:Histones; D000077209:Decitabine; D020170:Caspase 1; D001374:Azacitidine