• Journal of Life Science
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• v.19 no.12
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• pp.1787-1793
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• 2009

To investigate whether caffeic acid phenethyl ester (CAPE) could affect cancer cell viabilities and gene expression, human colorectal HCT116 cells were incubated with CAPE. CAPE decreased cancer cell viabilities and induced apoptosis in a dose-dependent manner. To analyse differently expressed genes by CAPE, we performed oligo DNA microarray analysis. We found that 266 genes were up-regulated more than twofold, whereas 143 genes were down-regulated more than twofold by 24 hr of treatment with $20{\mu}M$ CAPE. Among the up-regulated genes, we selected 3 genes (NSAID activated gene-1 [NAG-1], cyclin-dependent kinase inhibitor 1A [CDKN1A, p21] and growth arrest and DNA-damage-inducible alpha [GADD45A]) and performed reverse-transcription PCR to confirm microarray data. In addition, we found that CAPE increased NAG-1 gene and NAG-1 protein expression in a dose-dependent manner. And, several other phytochemicals (resveratrol, genistein, daidzein and capsaicin) also could induce NAG-1 expression in human colorectal HCT116 cells. However, CAPE was the highest inducer of NAG-1, even in low concentrations. Overall, these results imply that cancer cell death by CAPE is closely related with over-expression of NAG-1.

• Microbiology and Biotechnology Letters
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• v.38 no.4
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• pp.442-447
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• 2010

We investigated anti-cancer and anti-proliferative activity of allicin and analyzed global gene expression changes by allicin treatment in human colorectal HCT116 cells. As a result, allicin decreased cell viabilities in a dose and time-dependent manner and induced apoptosis. Oligo DNA microarray analysis, we found that 7,840 genes were up-regulated more than 2-folds, whereas 10,010 genes were down-regulated more than 2-folds by $50\;{\mu}M$ allicin treatment. To confirm specific gene expressions, we performed RT-PCR. Consistent with the results of DNA microarray analysis, allicin dramatically induced ATF3 and NAG1 gene expression. Interestingly, NAG-1 protein expression was dependent on p53 presence. Taken together, our present results increase the knowledge of the molecular mechanism of anti-cancer and anti-proliferative activity mediated by allciin in human colorectal cancer cell.

• Journal of Gastric Cancer
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• v.6 no.1
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• pp.25-30
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• 2006

Purpose: The EphB2 receptor, a member of the receptor tyrosine kinase family, is a target gene of the Wnt signaling pathway and may achieve a tumor suppressor function through regulation of cell growth and migration. Our aim was to determine whether an altered expression of EphB2 might be associated with gastric cancer development and, if so, to determine to which pathologic parameter it is linked. Materials and Methods: For the construction of the gastric cancer tissue microarray, 83 paraffin-embedded tissues containing gastric cancer areas were cored 3 times and transferred to the recipient master block. The expression patterns of EphB2 were examined on tissue microarray slides by using immunohistochemistry and were compared using pathologic parameters, including histological type, depth of invasion, lymph node metastatsis, and peritoneal dissemination. Results: The EphB2 protein was expressed in the normal gastric mucosal epithelium, especially in the bottom of the mucosa. We found loss of EphB2 expression in 30 (36.1%) of the 83 gastric cancer tissues. Statistically, loss of EphB2 expression was more common in gastric cancer with lymph-node metastasis. There was no significant correlation between EphB2 expression and depth of invasion, histologic type, or peritoneal dissemination. Conclusion: Our findings suggest that loss of EphB2 expression may represent a critical step in gastric carcinogenesis.

• Journal of Life Science
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• v.21 no.9
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• pp.1219-1225
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• 2011

Phytochemicals, non-nutrient chemicals derived from plants, have been shown to have anti-inflammation, anti-oxidation, and chemopreventive effects. In the current study, we investigated whether five different phytochemicals (resveratrol, genistein, epicatechin gallate, diallyl disulfide, and caffeic acid phenethyl ester) alter cell growth and gene expression in human colorectal cancer HCT116 cells. Using a cell viability assay, we found that each of the phytochemicals tested inhibited HCT116 cell growth in a dose-dependent manner. Additionally, using human oligo DNA microarray analysis, we found that only six genes were commonly up-regulated and seven genes were commonly down-regulated in response to each phytochemical treatment. For the commonly up-regulated genes, the microarray analysis was confirmed by reverse transcription.PCR using gene-specific primers. In addition, NAG-1 protein was up-regulated by all treated phytochemcials. The results of this study may help to enhance our understanding of the general molecular mechanisms of chemoprevention that are mediated by phytochemicals in human colorectal cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.12
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• pp.6239-6244
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• 2012

Background: The basal cell carcinoma (BCC) is the most common non-melanoma skin cancer (NMSK). BCC might develop because of the faulty cell cycle arrest. $p15^{INK4b}$ is a tumor suppressor gene, involved in cell cycle arrest and inactivated in most human cancers. The role of $p15^{INK4b}$ protein expression in the genesis of BCC is as yet unknown. In a previous study we showed the absence of $p15^{INK4b}$ expression in the majority of tissue microarray cores of cutaneous squamous cell carcinoma (SCCs), another type of non-melanoma skin cancer, indicating that $p15^{INK4b}$ could possibly be involved in the pathogenesis of cutaneous SCC. The aim of this study was to investigate $p15^{INK4b}$ protein expression in BCCs. Materials and Method: Protein expression of $p15^{INK4b}$ in 35 cases of BCC tissue arrays and 19 cases of normal human skin tissue was studied using an immunohistochemical approach. Results: The expression of $p15^{INK4b}$ was not significantly different in the BCC cases as compared with normal human skin (p=0.356; p>0.05). In addition, there were no significant relationship between clinicopathologic variables of patients (age and sex) and $p15^{INK4b}$ protein expression. Conclusions: Our finding may indicate that $p15^{INK4b}$ protein expression does not play a role in the genesis of BCC.

• Journal of Yeungnam Medical Science
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• v.24 no.1
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• pp.24-40
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• 2007

Background : Accumulating evidence shows that interleukin(IL)-1 plays a critical role in inflammation and connective tissue destruction observed in both osteoarthritis and rheumatoid arthritis. IL-1 induces gene expression related to cytokines, chemokines and matrix metalloproteinases by activation of many different transcription factors. Materials and Methods : The chondrosarcoma cell line, SW1353, is known to be a valuable in vitro system for investigating catabolic gene regulation by IL-$1{\beta}$ in chondrocytic cells. To explore and analyze the changes in gene expression by IL-1 responsible for arthritis, SW1353 was treated with IL-1 for 1, 6 and 24 h and then total RNAs were purified for each time. The changes in gene expression were analyzed with 17k human cDNA microarrays and validated by semi-quantitative RT-PCR. Results : Greater than a two-fold change was observed in 1,200 genes including metallothioneins, matrix metalloproteinases, extracellular matrix proteins, antioxidant proteins, cytoskeleton proteins, cell cycle regulatory proteins, proteins for cell growth and apoptosis, signaling proteins and transcription factors. These changes appeared to be correlate with the pathophysiological changes observed in early osteoarthritis. Conclusion : cDNA microarray analysis revealed a marked variability in gene expression, and provided insight into the overall molecular changes. The result of this study provide initial information for further studies to identify therapeutic targets in osteoarthritis pathogenesis.

• Korean Journal of Microbiology
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• v.51 no.1
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• pp.39-47
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• 2015

Secondary metabolism in actinomycetes has been known to be controlled by a small molecule, ${\gamma}$-butyrolactone autoregulator, the binding of which to each corresponding receptor leads to the regulation of the transcriptional expression of the secondary metabolites. We expected that expression of an autoregulator receptor or a pleiotropic regulator in a non-host was to be gained insight of effective production of new metabolic materials. In order to study the function of the receptor protein (seaR), which is isolated from Saccharopolyspora erythraea, we introduced the seaR gene to Streptomyces coelicolor A3(2) as host strains. An effective transformation procedure for S. coelicolor A3(2) was established based on transconjugation by Escherichia coli ET12567/pUZ8002 with a ${\varphi}C31$-derived integration vector, pSET152, which contained int, oriT, attP and $ermEp^*$ (erythromycin promotor). Therefore, the pEV615 was introduced into S. coelicolor A3(2) by conjugation and integrated at the attB locus in the chromosome of the recipients by the ${\varphi}C31$ integrase (int) function. Exconjugant of S. coelicolor A3(2) containing the seaR gene was confirmed by PCR and transcriptional expression of the seaR gene in the transformant was analyzed by RT-PCR. In case of S. coelicolor A3(2), a phenotype microarray was used to analyze the phenotype of transformant compared with wild type by seaR expression. After that, in order to confirm the accuracy of the results obtained from the phenotype microarray, an antimicrobial susceptibility test was carried out. This test indicated that sensitivity of the transformant was higher than wild type in tetracycline case. These results indicated that some biosynthesis genes or resistance genes for tetracycline biosynthesis in transformant might be repressed by seaR expression. Therefore, subsequent experiments, analysis of transcriptional pattern of genes for tetracycline production or resistance, are needed to confirm whether biosynthesis genes or resistance genes for tetracycline are repressed or not.

• Journal of Gastric Cancer
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• v.5 no.3 s.19
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• pp.200-205
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• 2005

Purpose: KLF4, a member of the KLF family, is a zinc finger tumor suppressor protein that is critical for gastric epithelial homeostasis. Our aim was to determine whether the altered expression of KLF4 might be associated with gastric cancer development and, if so, to determine to which pathologic parameter it is linked. Materials and Methods: For the construction of the gastric cancer tissue microarray, 84 paraffin-embedded tissues containing gastric cancer areas were cored 3 times and transferred to the recipient master block. The expression pattern of KLF4 was examined on tissue microarray slides by using immunohistochemistry and was compared with pathologic parameters, including histologic type, depth of invasion, lymph node metastasis, and peritoneal dissemination. Results: The KLF4 protein was expressed in cytoplasm and nucleus of superficial and foveolar epithelial cells in the normal gastric mucosa. We found markedly reduced or loss of KLF4 expression in 43 (51.2%) of the 84 gastric cancer tissues. There was no significant correlation between KLF4 expression and pathologic parameters, including histologic type, depth of invasion, lymph node metastasis and peritoneal dissemination. Conclusion: Our findings suggest that altered expression of KLF4 may contribute to abnormal regulation of gastrointestinal epithelial cell growth and differentiation and to the development of Korean gastric cancer, as an early event.

• Journal of Gastric Cancer
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• v.3 no.2
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• pp.88-92
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• 2003

Purpose: Mounting evidence suggests that alterations of Akt/protein kinase B (PKB) play an important role in tumorigenesis. Phosphorylated Akt regulates many of the key effector molecules involved in apoptosis, angiogenesis, and cell-cycle progression during tumorigenesis. The expression of phosphorylated Akt has been described in some human malignancies, but not in primary human gastric cancer. The purpose of this study was to explore the expression status of phosphorylated Akt protein in gastric carcinomas. Materials and Methods: In the current study, we analyzed the expression of phosphorylated Akt protein in 60 advanced gastric adenocarcinomas by using immunohistochemistry and a tissue microarray approach. Results: Immunopositivity (defined as $\geq\30\%$) was observed for the phosphorylated Akt in 42 ($70\%$) of the 60 cancers. Normal gastric mucosal cells showed no or weak expression of phosphorylated Akt protein. Conclusion: Taken together, these results indicate that Akt is frequently activated in gastric adenocarcinoma cells and suggest that phosphorylayed Akt may play a role in the development of human gastric adenocarcinomas.

• Proceedings of the Korean Society for Bioinformatics Conference
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• 2003.10a
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• pp.164-169
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• 2003

In this paper, we propose the integrated Bayesian network framework to reconstruct genetic regulatory networks from genome expression data. The proposed model overcomes the dimensionality problem of multivariate analysis by building coherent sub-networks from confined gene clusters and combining these networks via intermediary points. Gene Shaving algorithm is used to cluster genes that share a common function or co-regulation. Retrieved clusters incorporate prior biological knowledge such as Gene Ontology, pathway, and protein protein interaction information for extracting other related genes. With these extended gene list, system builds genetic sub-networks using Bayesian network with MDL score and Sparse Candidate algorithm. Identifying functional modules of genes is done by not only microarray data itself but also well-proved biological knowledge. This integrated approach can improve there liability of a network in that false relations due to the lack of data can be reduced. Another advantage is the decreased computational complexity by constrained gene sets. To evaluate the proposed system, S. Cerevisiae cell cycle data [1] is applied. The result analysis presents new hypotheses about novel genetic interactions as well as typical relationships known by previous researches [2].