HGF/SF Regulates Expression of Apoptotic Genes in MCF‐10A Human Mammary Epithelial Cells
Catherine LeroyJulien DeheuninckSylvie ReveneauBénédicte FoveauZongling JiCéline VillenetSabine QuiefDavid TulasneJean‐Pierre KerckaertVéronique Fafeur
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Abstract: Hepatocyte growth factor/scatter factor (HGF/SF) induces scattering, morphogenesis, and survival of epithelial cells through activation of the MET tyrosine kinase receptor. HGF/SF and MET are involved in normal development and tumor progression of many tissues and organs, including the mammary gland. In order to find target genes of HGF/SF involved in its survival function, we used an oligonucleotide microarray representing 1,920 genes known to be involved in apoptosis, transcriptional regulation, and signal transduction. MCF‐10A human mammary epithelial cells were grown in the absence of serum and treated or not with HGF/SF for 2 h. Total RNA was reverse‐transcribed to cDNA in the presence of fluorescent Cy3‐dUTP or Cy5‐dUTP to generate fluorescently labeled cDNA probes. Microarrays were performed and the ratios of Cy5/Cy3 fluorescence were determined. The expression of three apoptotic genes was modified by HGF/SF, with A20 being upregulated, and DAXX and SMAC being downregulated. These changes of expression were confirmed by real‐time quantitative PCR. According to current‐knowledge, A20 is antiapoptotic and SMAC is proapoptotic, while a pro‐ or antiapoptotic function of DAXX is controversial. The fact that HGF/SF upregulates an antiapoptotic gene (A20) and downregulates a proapoptotic gene (SMAC) is in agreement with its survival effect in MCF‐10A cells. This study identified novel apoptotic genes regulated by HGF/SF, which can contribute to its survival effect.Cite
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Objective Microarray was used to study the toxic effect of Sudan I on the gene expression profile of human lymphocytes, with emphasis on the gene expression and tumorigenesis.Methods Peripheral blood lymphocytes were treated with 10 -5 mol/L Sudan I for 8 h. The total RNA from cells of the subjects of the treated group and the control group were isolated, then they were reversely transcribed and labeled with fluorescence dyes, and finally hybridized with human whole genome microarray (about 35,000 spots). Microarray data was extracted after microarray scanning, and the genes correlating to tumor were screened out and analyzed by bioinformatics.Results Among 306 up-regulated genes, 11 genes were found to be related to tumor formation. 181 genes were down-regulated, of which 16 genes were related with tumor development.Conclusion Sudan I could affect gene expression of lymphocytes, and reduced gene expression is an indicator of tumor development.
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To study the genes differentially expressed in the liver of Kkay diabetic and normal mice by genomic-scale gene expression analysis.cDNA microarray chips containing 8,192 cDNAs were used to explore the gene expression pattern of Kkay mouse liver.One hundred and fifty-four genes were screened out, including 68 complete cDNAs and expressed sequence tags, and among them 40 genes were up-regulated and 114 genes were down-regulated respectively.Most of the gene expression analysis results were consistent with previous study, and the gene expression pattern of Kkay mouse based on cDNA microarray could be used for high-throughout screening out the genes associated with type 2 diabetes.
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Microarray technology has become an indispensable tool for monitoring the levels of gene expression in a given organism through organization, analysis, interpretation, and utilization of biological sequences.Importantly, preliminary microarray gene expression differs from experimentally validated gene expression.Generally, microarray analysis of gene expression in microglial cells is used to identify genes in the brain and spinal cord that are responsible for the onset of neurodegenerative diseases; these genes are either upregulated or downregulated.In the present study, 770 genes identified in prior publications, including experimental studies, were analyzed to determine whether these genes encode novel disease genes.Among the genes published, 340 genes were matched among multiple publications, whereas 430 genes were mismatched; the matched genes were presumed to have the greatest likelihood of contributing to neurodegenerative diseases and thus to be potentially useful target genes for treatment of neurodegenerative diseases.In protein and mRNA expression studies, matched and mismatched genes showed 99% and 97% potentiality, respectively.In addition, some genes identified in microarray analyses were significantly different from those in experimentally validated expression patterns.This study identified novel genes in microglial cells through comparative analysis of published microarray and experimental data on neurodegenerative diseases.
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To identify the genes expressed differentially in the regenerating rat liver in a short interval successive partial hepatectomy (SISPH), and to analyze their expression profiles.Five hundred and fifty-one elements selected from subtractive cDNA libraries were conformed to a cDNA microarray (cDNA chip). An extensive gene expression analysis following 0-36-72-96-144 h SISPH was performed by microarray.Two hundred and sixteen elements were identified either up- or down-regulated more than 2-fold at one or more time points of SISPH. By cluster analysis and generalization analysis, 8 kinds of ramose gene expression clusters were generated in the SISPH. Of the 216 elements, 111 were up-regulated and 105 down-regulated. Except 99 unreported genes, 117 reported genes were categorized into 22 groups based on their biological functions. Comparison of the gene expression in SISPH with that after partial hepatectomy (PH) disclosed that 56 genes were specially altered in SISPH, and 160 genes were simultaneously up-regulated or down-regulated in SISPH and after PH, but in various amount and at different time points.Genes expressed consistently are far less than that intermittently; the genes strikingly increased are much less than that increased only 2-5 fold; the expression trends of most genes in SISPH and in PH are similar, but the expression of 56 genes is specifically altered in SISPH. Microarray combined with suppressive subtractive hybridization can in a large scale effectively identify the genes related to liver regeneration.
Suppression subtractive hybridization
Liver Regeneration
Gene chip analysis
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Exercise training causes some physiological cardiovascular adaptations, which act to enhance cardiac and vascular functions at rest and during exercise. However, the molecular mechanisms of these adaptations are unclear. We investigated gene expression profiles of exercise training-induced cardiovascular adaptations. In the experiment, rats exercised on a treadmill for 4 or 8 weeks (4WT and 8WT). The differences in expression levels of 3,800 genes in the heart and abdominal aorta of sedentary control and exercise-trained rats were compared by the microarray analysis. Of the 3,800 genes analyzed in the microarray analyses, in the heart, a total of 45 genes (upregulation of 3 genes and downregulation of 42 genes) in the 4WT and 74 genes (upregulation of 50 genes and downregulation of 24 genes) in the 8WT displayed altered gene expression with exercise training. In the aorta, a total of 57 genes (upregulation of 35 genes and downregulation of 24 genes) in the 4WT and 31 genes (upregulation of 12 genes and downregulation of 19 genes) in the 8WT displayed altered gene expression with exercise training. Thus exercise training caused an alteration of many genes expression in the heart and aorta. The alteration of many genes expression in the heart observed in 8WT, whereas that in the aorta induced in 4WT. The observed difference in the change of the gene expression in the time course between the heart and aorta suggests that there may be a difference in the time course of exercise-induced physiological adaptation in the heart and aorta (e.g., formation of physiological cardiac hypertrophy and enhancement of arterial compliance).
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Sexual differentiation of the rodent brain is recognized to involve transcriptional activation of multiple genes induced by gonadal steroids at developmental stages. To identify the genes differing in expression level between sexes, we analyzed gene expression in male and female rat hypothalami at postnatal day 5 by means of a cDNA microarray consisting of 2352 genes. By comparing the expression pattern between sexes, we identified 12 male-enriched genes and 20 female-enriched genes. Among them, the expression pattern of 1 male-enriched gene, jagged homolog 1, and those of 2 female-enriched genes, p27Kip1 and p130, were confirmed to be consistent with microarray data by RT-PCR. Investigation of these genes should help to elucidate the molecular and cellular mechanisms underlying sexual differentiation of the rodent central nervous system.
Sexual Differentiation
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Although it is now well known that some diseased areas, such as cancer nests, inflammation loci, and infarction areas, are acidified, little is known about cellular signal transduction, gene expression, and cellular functions under acidic conditions. Our group showed that different signal proteins were activated under acidic conditions compared with those observed in a typical medium of around pH 7.4 that has been used until now. Investigations of gene expression under acidic conditions may be crucial to our understanding of signal transduction in acidic diseased areas. In this study, we investigated gene expression in mesothelioma cells cultured at an acidic pH using a DNA microarray technique. After 24 h culture at pH 6.7, expressions of 379 genes were increased more than twofold compared with those in cells cultured at pH 7.5. Genes encoding receptors, signal proteins including transcription factors, and cytokines including growth factors numbered 35, 32, and 17 among the 379 genes, respectively. Since the functions of 78 genes are unknown, it can be argued that cells may have other genes for signaling under acidic conditions. The expressions of 37 of the 379 genes were observed to increase after as little as 2 h. After 24 h culture at pH 6.7, expressions of 412 genes were repressed more than twofold compared with those in cells cultured at pH 7.5, and the 412 genes contained 35, 76, and 7 genes encoding receptors, signal proteins including transcription factors, and cytokines including growth factors, respectively. These results suggest that the signal pathways in acidic diseased areas are different, at least in part, from those examined with cells cultured at a pH of around 7.4.
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Abstract Objectives/Hypothesis: We investigated acute changes in extracellular matrix gene expression and histologic changes in the deposition of collagen and hyaluronan (HA) from hepatocyte growth factor (HGF) treatment of the aged rat vocal fold. We hypothesized that: 1) HGF induces matrix metalloproteinase gene expression, which might contribute to the downregulation of collagen; and 2) HGF induces hyaluronan synthase (HAS) gene expression, which might play a role in the upregulation of extracellular matrix HA. Study Design: Prospective animal study. Methods: Fifteen, 18‐month‐old, Sprague‐Dawley rats were involved in this study. For gene expression analyses, 10 rats were divided into two groups and received serial injections of sham (saline) or HGF (2 ng/μL) and sacrificed 2 weeks after the initial injection to investigate acute changes in extracellular matrix gene expression. A separate group of five animals received the above treatment and were sacrificed 4 weeks after the initial injection to investigate histologic changes in the deposition of collagen and HA. Results: Real‐time polymerase chain reaction revealed significantly upregulated matrix metalloproteinase(MMP)‐2, ‐9, and HAS‐3 messenger RNA (mRNA) expression and significantly downregulated procollagen type I mRNA expression in the HGF‐treatment group, compared to the sham‐treatment group. Histologic staining revealed significantly reduced collagen deposition and increased deposition of HA in the HGF‐treated vocal fold, compared to the sham‐treated vocal fold. Conclusions: HGF induced the upregulation of MMP‐2, ‐9, and HAS‐3, and downregulated the expression of procollagen type I. Histologically, aged vocal folds treated with HGF revealed decreased collagen deposition, and increased deposition of HA, compared to sham‐treated vocal folds. Laryngoscope, 2009
Matrix Metalloproteinase 3
Procollagen peptidase
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