• Molecular & Cellular Toxicology
• /
• 제3권4호
• /
• pp.231-237
• /
• 2007

Exposure to DNA-damaging agents can elicit a variety of stress-related responses that may alter the expression of genes associated with numerous biological pathways. We used 19 k whole human genome chip to detect gene expression profiles and potential signature genes in human normal hepatocytes (THLE-3) by treatment of five direct acting mutagens, furylfuramide (AF-2), N-nitroso-N-methylurea (MNU), methylmethanesulfonate (MMS), 4-nitroquinoline-N-oxide (4-NQO) and 2-nitrofluorene (2NF) of the $IC_{20}$ concentration for 3 h. Fifty one up-regulated common genes and 45 down-regulated common genes above 1.5-fold by five direct-acting mutagens were identified by clustering analysis. Many of these changed genes have some association with apoptosis, control of cell cycle, regulation of transcription and signal transduction. Genes related to these functions, as TP73L, E2F5, MST016, SOX5, MAFB, LIF, SII3, TFIIS, EMR1, CYTL1, CX3CR1 and RHOH are up-regulated. Down-regulated genes are ALOX15B, xs155, IFITM1, BATF, VAV2, CD79A, DCDC2, TNFSF8 and KOX8. We suggest that gene expression profiling on mutagens by toxicogenomic analysis affords promising opportunities to reveal potential new mechanistic markers of genotoxicity.

• Reproductive and Developmental Biology
• /
• 제31권4호
• /
• pp.221-226
• /
• 2007

Embryonic stem (ES) cells are known to have an infinite proliferation and pluripotency that are associated with complex processes. The objective of this study was to examine expression of genes differentially regulated during differentiation of human ES cells by suppression subtractive hybridization (SSH). Human ES cells were induced to differentiate into neural precursor cells via embryoid body. Neural precursor cells were isolated physically based on morphological criteria. Immunocytochemical analysis showed expression of pax6 in neural precursor cells, confirming that the isolated cells were neural precursor cells. Undifferentiated human ES cells and neural precursor cells were subject to the SSH. TPX2 (Targeting Protein for Xklp2 (Xenopus centrosomal kinesin-like protein 2)) was identified, cloned and analyzed during differentiation of human ES cells into neural lineages. Expression of TPX2 was gradually down-regulated in embryoid bodies and neural precursor cells relative to undifferentiated ES cells. Targeting Protein for Xklp2 has been shown to be involved in cell division by interaction with microtubule development in cancer cells. Taken together, result of this study suggests that TPX2 may be involved in proliferation and differentiation of human ES cells.

• Molecular & Cellular Toxicology
• /
• 제3권1호
• /
• pp.60-67
• /
• 2007

Gentamicin is a broad-spectrum aminoglycoside antibiotic used in the treatment of bacterial infection. Although side effects of gentamicin such as nephrotoxicity and ototoxicity have been investigated, the information on the hepatic effects of gentamicin is still limited. In the present study, gene expression profiles were analyzed in the liver of gentamicin treated mice using Affymetrix GeneChip$^{(R)}$ Mouse Expression 430A 2.0 Array. Totally, 400 genes were identified as being either up- or down-regulated over 1.5-fold changes (P<0.01) in the liver of gentamicin treated mice. Among these deregulated genes, 16 up-regulated genes mainly involved in transport (Kif5b, Pex14, Rab14, Clcn3, and Necap1) and 20 down-regulated genes involved in lipid and other metabolisms (Hdlbp, Gm2a, Uroc1, and Dak) were selected using k-means clustering algorithm. The functional classification of differentially expressed genes represented that several stress-related genes were regulated in the liver by gentamicin treatment. This data may contribute in understanding the molecular mechanism in the liver of gentamicin treated mice.

• Asian Pacific Journal of Cancer Prevention
• /
• 제13권8호
• /
• pp.3997-4000
• /
• 2012

MicroRNAs (miRNAs) play roles in the clinic, both as diagnostic and therapeutic tools. The identification of relevant microRNAs is critically required for ovarian cancer because of the prevalence of late diagnosis and poor treatment options currently. To identify miRNAs involved in the development or progression of ovarian cancer, we analyzed gene expression profiles downloaded from Gene Expression Omnibus. Comparison of expression patterns between carcinomas and the corresponding normal ovarian tissues enabled us to identify 508 genes that were commonly up-regulated and 1331 genes that were down-regulated in the cancer specimens. Function annotation of these genes showed that most of the up-regulated genes were related to cell cycling, and most of the down-regulated genes were associated with the immune response. When these differentially expressed genes were mapped to MiRTarBase, we obtained a total of 18 key miRNAs which may play important regulatory roles in ovarian cancer. Investigation of these genes and microRNAs should help to disclose the molecular mechanisms of ovarian carcinogenesis and facilitate development of new approaches to therapeutic intervention.

• 대한의생명과학회지
• /
• 제18권1호
• /
• pp.1-9
• /
• 2012

Differentially expressed genes by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) were identified in order to evaluate them as dioxin-sensitive markers and crucial signaling molecules to understand dioxin-induced toxic mechanisms in human bronchial cells. Gene expression profiling was analyzed by cDNA microarray and ten genes were selected for further study. They were cytochrome P450, family 1, subfamily B, polypeptide 1 (CYP1B1), S100 calcium binding protein A8 (calgranulin A), S100 calcium binding protein A9 (calgranulin B), aldehyde dehydrogenase 1 family, member A3 (ALDH6) and peroxiredoxin 5 (PRDX5) in up-regulated group. Among them, CYP1B1 was used as a hallmark for dioxin and sharply increased by TCDD exposure. Down-regulated genes were IK cytokine, interferon-induced protein with tetratricopeptide repeats 1 (IFIT1), nuclease sensitive element binding protein 1 (NSEP1), protein tyrosine phosphatase type VI A, member 1 (PTP4A1), ras oncogene family 32 (RAB32). Although up-regulated 4 genes in microarray were coincided with northern hybridization, down-regulated 5 genes showed U-shaped expression pattern which is sharply decreased at lower doses and gradually increased at higher doses. These results introduce some of TCDD-responsive genes can be sensitive markers against TCDD exposure and used as signaling cues to understand toxicity initiated by TCDD inhalation in pulmonary tissues.

• 한방안이비인후피부과학회지
• /
• 제22권1호
• /
• pp.11-32
• /
• 2009

Objective : This study was designed to investigate anti-cancer and whitening activities (LC). So it was investigated the effects of LC on proliferation rates of melanoma genetic profile by LC. Methods : The genetic profile for the effect of LC on human derived melanoma cell, SK-MEL-2, was measured using microarray technique, and the functional analysis on these genes were conducted. Total 441 genes were up-regulated and 830 genes down-regulated in cells treated with LC. Genes induced or suppressed by LC were all mainly concerned with basic signalling pathways, which are involved in cell growth, differentiation and migration. Especially, many genes, which are related in apoptosis and cell cycle arrest were up-regulated by treatment with LC, and genes related in cell cycle were down-regulated. Result : The network of total protein interactions were identified by using cytoscape program, and some key molecules, such as BCL2L1, SIN3A, SMAD2 and c-myc that can be used for elucidation of therapeutical mechanism of medicine in the future. Conclusion : These results suggest possibility of LC as addition drug and whitening cosmetics. In addition, it was also suggested that related mechanisms are involved in BCL2L1, SIN3A, SMAD2 and c-myc related signalling pathways.

• Genomics & Informatics
• /
• 제20권1호
• /
• pp.7.1-7.13
• /
• 2022

2-Methoxy-1,4-naphthoquinone (MNQ) has been shown to cause cytotoxic towards various cancer cell lines. This study is designed to investigate the regulatory effect of MNQ on the key cancer genes in mitogen-activated protein kinase, phosphoinositide 3-kinase, and nuclear factor κB signaling pathways. The expression levels of the genes were compared at different time point using polymerase chain reaction arrays and Ingenuity Pathway Analysis was performed to identify gene networks that are most significant to key cancer genes. A total of 43 differentially expressed genes were identified with 21 up-regulated and 22 down-regulated genes. Up-regulated genes were involved in apoptosis, cell cycle and act as tumor suppressor while down-regulated genes were involved in anti-apoptosis, angiogenesis, cell cycle and act as transcription factor as well as proto-oncogenes. MNQ exhibited multiple regulatory effects on the cancer key genes that targeting at cell proliferation, cell differentiation, cell transformation, apoptosis, reduce inflammatory responses, inhibits angiogenesis and metastasis.

• Asian Pacific Journal of Cancer Prevention
• /
• 제13권11호
• /
• pp.5433-5438
• /
• 2012

Background: Hepatocellular carcinoma (HCC) is a common and aggressive malignancy. Despite of the improvements in its treatment, HCC prognosis remains poor due to its recurrence after resection. This study provides complete genetic profile for Egyptian HCC. Genome-wide analyses were performed to identify the predictive signatures. Patients and Methods: Liver tissue was collected from 31 patients with diagnosis of HCC and gene expression levels in the tumours and their adjacent non-neoplastic tissues samples were studied by analyzing changes by microarray then correlate these with the clinico-pathological parameters. Genes were validated in an independent set by qPCR. The genomic profile was associated with genetic disorders and cancer focused on gene expression, cell cycle and cell death. Molecular profile analysis revealed cell cycle progression and arrest at G2/M, but progression to mitosis; unregulated DNA damage check-points, and apoptosis. Result: Nine hundred fifty eight transcripts out of the 25,000 studied cDNAs were differentially expressed; 503 were up-regulated and 455 were down-regulated. A total of 19 pathways were up-regulated through 27 genes and 13 pathways were down-regulated through 19 genes. Thirty-seven genes showed significant differences in their expression between HCC cases with high and low Alpha Feto Protein ($AFP{\geq}600$ IU/ml). The validation for the microarray was done by real time PCR assay in which PPP3CA, ATG-5, BACE genes showed down-regulation and ABCG2, RXRA, ELOVL2, CXR3 genes showed up-regulation. cDNA microarrays showed that among the major upregulated genes in HCC are sets. Conclusion: The identified genes could provide a panel of new diagnostic and prognostic aids for HCC.

• Asian Pacific Journal of Cancer Prevention
• /
• 제13권2호
• /
• pp.641-646
• /
• 2012

In our recent report on gene expression in gastric cancer we identified the endo-sulfatase Sulf-1 gene to be up-regulated in gastric tumors relative to apparently normal (AN), and paired normal (PN) gastric tissue samples. In the present report we investigate the protein expression levels of Sulf-1 gene in gastric tumors, AN and PN samples using tissue microarray (TMA) and immunohistochemistry. Expression data was collected from two sets of TMA's containing replicate sections of tissue samples. Scoring data from TMA set-1 revealed a significant difference in Sulf-1 immunoreactivity between tumors and "normals" (PN and AN) (p-value = 0.001928). Also, Sulf-1 expression in tumors was also significantly different from either PN (p-value = 0.019) or AN (p-value = 0.006) samples. Similar results were obtained from analysis of scoring data from the second set of arrays. Comparison of mRNA expression and protein expression in gastric tumor tissues revealed that in 6/20 (30%) tumor samples showed up-regulated protein expression concordant with over-expression of mRNA. However, a discord with mRNA being over-expressed relative to down regulated protein expression was observed in majority 14/20 (70%) of tumor samples. Our study indicates down regulation of Sulf-1 protein expression in gastric tumors relative to PN and AN samples which is discordant with mRNA over-expression seen in tumors.

• 대한한방내과학회지
• /
• 제30권3호
• /
• pp.594-603
• /
• 2009

Objectives : ICH breaks down blood vessels within the brain parenchyma, which finally leads to neuronal loss, drugs to treat ICH have not yet been established. In this experiment, we measured the effect of Woowhangchongshim-won (WWCSW) on intracerebral hemorrhage (ICH) in rat using microarray technology. Methods : We measured the effect of WWCSW on ICH in rat using microarray technology. ICH was induced by injection of collagenase type IV, and total RNA was isolated. Image files of microarray were measured using a ScanArray scanner, and the criteria of the threshold for up- and down-regulation was 2 fold. Hierarchical clustering was implemented using CLUSTER and TREEVIEW program, and for Ontology analysis. GOSTAT program was applied in which p-value was calculated by Chi square or Fisher's exact test based on the total array element. Results : WWCSW-treatment restored the gene expression altered by ICH-induction in brain to the levels of 76.0% and 70.1% for up- and down-regulated genes, respectively. Conclusion : Co-regulated genes by ICH model of rat could be used as molecular targets for therapeutic effects of drug including WWCSW. That is, the presence of co-regulated genes may represent the importance of these genes in ICH in the brain and the change of expression level of these co-regulated genes would also indicate the functional change of brain tissue.