ABSTRACT
Intrahepatic cholangiocarcinoma (ICC), a malignant tumor derived from the bile duct epithelium, is one of the leading causes of death from cancer, worldwide. However, the mechanisms related to it remain largely unknown. In this study, an analysis of the gene expression profiles for ICC was done using the frequency of the ESTs obtained from nine cDNA libraries that constructed from 4 ICC cell lines and 4 normal liver tissues. One hundred and thirty-seven genes were identified as being either up- or down-regulated in human ICC cells. Thirty genes were randomly selected to confirm their differential expression in 4 human ICC cell lines and 5 ICC tissues compared to normal liver tissues by semi-quantitative RT-PCR. Among these genes, ANXA1, ANXA2, AMBP, and SERPINC1 were further verified by immunohistochemical analyses. In conclusion, these identified genes represent potential biomarkers for ICC and represent potential targets for elucidating the molecular mechanisms that are associated with ICC.
Subject(s)
Bile Duct Neoplasms/genetics , Cholangiocarcinoma/genetics , Gene Expression Regulation, Neoplastic , Genetic Predisposition to Disease , Liver/metabolism , Biomarkers, Tumor , Cell Line, Tumor , Down-Regulation , Expressed Sequence Tags , Gene Library , Humans , Molecular Sequence Data , Reverse Transcriptase Polymerase Chain Reaction , Up-RegulationABSTRACT
To elucidate the genetic events associated with gastric cancer, 124,704 cDNA clones were collected from 37 human gastric cDNA libraries, including 20 full-length enriched cDNA libraries of gastric cancer cell lines and tissues from Korean patients. An analysis of the collected ESTs revealed that 97,930 high-quality ESTs coalesced into 13,001 clusters, of which 11,135 clusters (85.6%) were annotated to known ESTs. The analysis of the full-length cDNAs also revealed that 4862 clusters (51.7%) contained at least one putative full-length cDNA clone with an initiation codon, with the average length of the 5' UTR of 140 bp. A large number appear to have a diverse transcription start site (TSS). An examination of the TSS of some genes, such as TEGT and GAPD, using 5' RACE revealed that the predicted TSSs are actually found in human gastric cancer cells and that several TSSs differ depending on the specific gastric cell line. Furthermore, of the human gastric ESTs, 766 genes (9.5%) were present as putative alternatively spliced variants. Confirmation of the predicted spliced isoforms using RT-PCR showed that the predicted isoforms exist in gastric cancer cells and some isoforms coexist in gastric cell lines. These results provide potentially useful information for elucidating the molecular mechanisms associated with gastric oncogenesis.
Subject(s)
Expressed Sequence Tags , Gene Expression Regulation, Neoplastic , Stomach Neoplasms/genetics , Transcription Initiation Site/physiology , 5' Untranslated Regions/genetics , Alternative Splicing , Amino Acid Sequence , Computational Biology , Gene Expression Profiling , Gene Library , Humans , Molecular Sequence Data , Sequence Alignment , Software Design , Stomach Neoplasms/metabolismABSTRACT
Trichostatin A (TSA) and S-adenosyl-L-homocysteine (AdoHcy) have been reported to affect histone modifications. To investigate the effects of two drugs that can reportedly affect chromatin remodeling, we analyzed the gene expression profiles of TSA and AdoHcy in a gastric cancer cell line using 14 K cDNA microarray. The significant analysis of microarray (SAM) identified 98 and 43 differentially expressed genes in TSA and AdoHcy treated sets, respectively, and selected genes were functionally classified. In the gastric cancer cell line, genes related to cell communication, cell growth/maintenance, and morphogenesis were highly expressed with TSA, and genes with cell growth/maintenance, metabolism, oxidoreductase activity were upregulated with AdoHcy. Genes downregulated with TSA included those controlling the cell cycle, cell growth/proliferation, DNA binding, and metabolism, whereas genes involved in calcium signaling, cell growth/proliferation, and metabolism were downregulated with AdoHcy. Furthermore, we identified the genes commonly expressed in both drug treatments. Compared to TSA, AdoHcy did not induce apoptosis in the SNU-16 gastric cancer cell line, and RT-PCR was performed for selective genes to confirm the microarray data. This gene expression profile analysis with TSA and AdoHcy should contribute to a greater understanding of the molecular mechanism of chromatin remodeling and cancer, and provide candidate genes for further studies involving the roles of histone modifications in gastric cancer.
