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Increased mRNA Levels (increased + mrna_level)

Distribution by Scientific Domains

Medical Sciences	75%

Selected Abstracts

Suppression of the TIG3 tumor suppressor gene in human ovarian carcinomas is mediated via mitogen-activated kinase-dependent and -independent mechanisms

INTERNATIONAL JOURNAL OF CANCER, Issue 6 2005
Kristina Lotz
Abstract The TIG3 gene is a retinoic acid inducible class II tumor suppressor gene downregulated in several human tumors and malignant cell lines. Diminished TIG3 expression correlates with decreased differentiation whereas forced expression of TIG3 suppresses oncogenic signaling pathways and subsequently induces differentiation or apoptosis in tumor cells. Analysis of TIG3 mRNA expression in a large set of cDNA pools derived from matched tumor and normal human tissues showed a significant downregulation of TIG3 in 29% of the cDNA samples obtained from ovarian carcinomas. Using in situ hybridization, we demonstrated expression of TIG3 in the epithelial lining of 7 normal ovaries but loss of TIG3 expression in 15/19 of human ovarian carcinoma tissues. In SKOV-3, CAOV-3 and ES-2 ovarian carcinoma cell lines, downregulation of TIG3 mRNA was reversible and dependent on an activated MEK-ERK signaling pathway. Re-expression of TIG3 mRNA in these cells upon specific interference with the MEK-pathway was correlated with growth inhibition of the cells. In OVCAR-3 and A27/80 ovarian carcinoma cells, TIG3 suppression is MEK-ERK independent, but expression could be reconstituted upon interferon gamma (IFN,) induction. Overexpression of TIG3 in A27/80 ovarian carcinoma cells significantly impaired cell growth and despite increased mRNA levels, TIG3 protein was hardly detectable. These results suggest that TIG3 is negatively regulated by an activated MEK-ERK signaling pathway. Further mechanisms must interfere with TIG3 expression that are independent of MEK and partially include interferon-responsive components. © 2005 Wiley-Liss, Inc. [source]

Expression of HSP72 after ELF-EMF exposure in three cell lines,

BIOELECTROMAGNETICS, Issue 7 2007
Eric Gottwald
Abstract It has been reported that magnetic fields with flux densities ranging from µT to mT are able to induce heat shock factor, HSP72 mRNA or heat shock proteins in various cells. In this study we investigated changes in the HSP72 mRNA transcription level in three cell lines (HL-60, H9c2, and Girardi heart cells) and in the intracellular HSP72 protein content in two cell lines (HL-60 and Girardi heart cells) after treatment schemes using electromagnetic fields with a flux density of 2 µT to 4 mT, a frequency of 50 Hz and exposure times from 15 to 30 min. None of the treatments or modalities showed any significant effect on the HSP72 protein level, although HSP72 mRNA could be induced, at least to some extent, with one of the parameter combinations in all cell lines tested. Obviously, HSP72 mRNA transcription and translation are not necessarily coupled in certain cells. This leads to the conclusion that electromagnetic field effects on HSP72 mRNA levels are not indicative for downstream effects unless increased mRNA levels can be correlated with increased HSP72 protein levels as well. Bioelectromagnetics 28:509,518, 2007. © 2007 Wiley-Liss, Inc. [source]

Solid dispersion of rutaecarpine improved its antihypertensive effect in spontaneously hypertensive rats

BIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 9 2008
Jin-Song Ding
Abstract It was reported previously that rutaecarpine produced a hypotensive effect in phenol-induced and 2-kidney, 1-clip hypertensive rats. However, the same dose of crude rutaecarpine did not produce significant hypotensive effects when applied to spontaneously hypertensive rats (SHR). In the present study, a different dose of rutaecarpine solid dispersion was administered intragastrically to SHR. The systolic blood pressure was monitored by the tail-cuff method with an electro-sphygmomanometer. The plasma concentration of rutaecarpine, calcitonin gene-related peptide (CGRP) and the mRNA levels of CGRP in dorsal root ganglion were determined. The results showed that administration of the solid dispersion significantly increased the blood concentration of rutaecarpine, accompanied by significant hypotensive effects in SHR in a dose-dependent manner. The levels of plasma CGRP were also elevated significantly, concomitantly with the increased mRNA levels in the dorsal root ganglion in a dose-dependent manner. It was concluded that a change of the dosage from the crude drug to solid dispersion could improve significantly the efficiency of rutaecarpine absorption and increase its plasma concentration. The anti-hypertensive effect exerted by rutaecarpine solid dispersion in SHR is mediated by CGRP. Copyright © 2008 John Wiley & Sons, Ltd. [source]

Elevated neutrophil membrane expression of proteinase 3 is dependent upon CD177 expression

CLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 1 2010
M. Abdgawad
Summary Proteinase 3 (PR3) is a major autoantigen in anti-neutrophil cytoplasmic antibodies (ANCA)-associated systemic vasculitis (AASV), and the proportion of neutrophils expressing PR3 on their membrane (mPR3+) is increased in AASV. We have shown recently that mPR3 and CD177 are expressed on the same cells in healthy individuals. In this study we try to elucidate mechanisms behind the increased mPR3 expression in AASV and its relationship to CD177. All neutrophils in all individuals were either double-positive or double-negative for mPR3 and CD177. The proportion of double-positive neutrophils was increased significantly in AASV and systemic lupus erythematosus patients. The proportion of mPR3+/CD177+ cells was not correlated to general inflammation, renal function, age, sex, drug treatment and levels of circulating PR3. AASV patients had normal levels of granulocyte colony-stimulating factor and granulocyte,macrophage colony-stimulating factor. Pro-PR3 was found to constitute 10% of circulating PR3 but none of the mPR3. We found increased mRNA levels of both PR3 and CD177 in AASV, but they did not correlate with the proportion of double-positive cells. In cells sorted based on membrane expression, CD177,mRNA was several-fold higher in mPR3+ cells. When exogenous PR3 was added to CD177-transfected U937 cells, only CD177+ cells bound PR3 to their membrane. In conclusion, the increased membrane expression of PR3 found in AASV is not linked directly to circulating PR3 or PR3 gene transcription, but is dependent upon CD177 expression and correlated with the transcription of the CD177 gene. [source]