OBJECTIVES: FOS-like antigen-2 (FOSL-2), a member of the FOS gene family, encode leucine zipper proteins that can heterodimerize with proteins of Jun family. Thus, activating protein (AP)-1 transcription factor is formed, has a crucial role in proliferation, differentiation and apoptosis of normal tissue as well as oncogenic transformation and progression. We performed an association study of single nucleotide polymorphisms (SNPs) in the FOSL-2 with papillary thyroid cancer (PTC). We also estimated the relationships between the SNPs and the clinicopathologic characteristics of PTC. METHODS: One promoter SNPs (rs925255) of FOSL-2 gene were genotyped with direct sequencing method in 94 PTC and 213 controls. PTC patients were dichotomized and compared with respect to clinical parameters of PTC. Genetic data were analyzed using Helixtree, SNPAnalyzer, SNPStats. Multivariate logistic regression analysis was fulfilled to evaluate the genetic effect with adjustment for age and sex. RESULTS: SNP (rs925255) in FOSL-2 showed a significant association (codominant 1 model [G/G vs. A/G]: odds ratio [OR], 0.531, 95% confidence interval [CI], 0.293 to 0.96, P=0.036; dominant model: OR, 0.50, 95% CI, 0.28 to 0.89, P=0.015) with PTC. The frequency of allele G in rs925255 was also significantly associated with PTC (OR, 0.59; 95% CI, 0.34 to 0.91; P=0.02). But we fail to prove significant association between this polymorphism (rs925255) and clinico-pathological parameters. CONCLUSION: Our findings suggest that the rs925255 SNP and its allele G show significant association with the PTC in Korean population.
Alleles ; Apoptosis ; Genes, fos ; Humans ; Leucine Zippers ; Logistic Models ; Methods ; Odds Ratio ; Polymorphism, Single Nucleotide ; Thyroid Gland* ; Thyroid Neoplasms* ; Transcription Factors

OBJECTIVETo investigate the relationship between c-fos gene and filamentous actin (F-actin) in MG-63 osteoblasts under cyclic tensile stress.

METHODSMG-63 osteoblasts were subjected to cyclic tensile stress (0.5 Hz, 2 000 microstrain) for 3, 6, and 12 h. The changes of c-fos gene were investigated by fluorescent quantitation polymerase chain reaction. Then the best loading time group was screened as the experimental group compared with 0 h group. The changes of F-actin and c-fos were investigated with or without cytochalasin D treatment.

RESULTSCyclic tensile stress induced high expression of c-fos mRNA, and peaked at 3 h. After loading, F-actin had a structure reorganization, but had no change in expression. After cytochalasin D treatment, the formation of stress fibers and the fluorescence intensity of F-actin cytoskeleton significantly reduced, meanwhile the c-fos mRNA expression was inhibited.

CONCLUSIONAfter loading, there is only structure reorganization for F-actin, and the expression has not any change. That means the remodeling F-actin is the existing one. F-actin reorganization is an important part in c-fos gene expression induced by stress.

Actin Cytoskeleton ; Actins ; Cytochalasin D ; Cytoskeleton ; Genes, fos ; Humans ; Microtubules ; Osteoblasts ; RNA, Messenger ; Stress, Mechanical

PURPOSE: Periodontal ligament (PDL) cell differentiation into osteoblasts is important in bone formation. Bone formation is a complex biological process and involves several tightly regulated gene expression patterns of bone-related proteins. The expression patterns of bone related proteins are regulated in a temporal manner both in vivo and in vitro. The aim of this study was to observe the gene expression profile in PDL cell proliferation, differentiation, and mineralization in vitro. METHODS: PDL cells were grown until confluence, which were then designated as day 0, and nodule formation was induced by the addition of 50 microg/mL ascorbic acid, 10 mM beta-glycerophosphate, and 100 nM dexamethasone to the medium. The dishes were stained with Alizarin Red S on days 1, 7, 14, and 21. Real-time polymerase chain reaction was performed for the detection of various genes on days 0, 1, 7, 14, and 21. RESULTS: On day 0 with a confluent monolayer, in the active proliferative stage, c-myc gene expression was observed at its maximal level. On day 7 with a multilayer, alkaline phosphatase, bone morphogenetic protein (BMP)-2, and BMP-4 gene expression had increased and this was followed by maximal expression of osteocalcin on day 14 with the initiation of nodule mineralization. In relationship to apoptosis, c-fos gene expression peaked on day 21 and was characterized by the post-mineralization stage. Here, various genes were regulated in a temporal manner during PDL fibroblast proliferation, extracellular matrix maturation, and mineralization. The gene expression pattern was similar. CONCLUSIONS: We can speculate that the gene expression pattern occurs during PDL cell proliferation, differentiation, and mineralization. On the basis of these results, it might be possible to understand the various factors that influence PDL cell proliferation, extracellular matrix maturation, and mineralization with regard to gene expression patterns.
Alkaline Phosphatase ; Anthraquinones ; Apoptosis ; Ascorbic Acid ; Biological Processes ; Bone Morphogenetic Proteins ; Cell Differentiation ; Cell Proliferation ; Dexamethasone ; Durapatite ; Extracellular Matrix ; Fibroblasts ; Gene Expression ; Genes, fos ; Genes, myc ; Glycerophosphates ; Humans ; Osteoblasts ; Osteocalcin ; Osteogenesis ; Periodontal Ligament ; Proteins ; Real-Time Polymerase Chain Reaction ; Transcriptome

OBJECTIVETo investigate the effects of pyrroloquinoline quinine (PQQ) on proliferation and expression of c-fos, c-jun, CREB and PCNA in cultured Schwann cells.

METHODSSchwann cells were cultured and purified in vitro. The purity of Schwann cells was identified by immunofluorescence of S-100. After synchronization of cell cycle by serum-free medium, different concentration of PQQ (0,1, 10, 100, 1,000, 10,000 nmol/L) were added into culture medium for 72 h. Flow cytometry was used to determine cell cycle. The content of c-fos, c-jun, and CREB mRNA were detected by RT-PCR, and the expression of PCNA protein was detected by Western blot.

RESULTSAfter PQQ treatment, the percentage of cells in G0/G1 phase decreased and the percentage of cells in S and G2/M phase increased. After treated by PQQ at concentration of 1-10,000nmol/L, content of c-fos,c-jun,CREB mRNA was increased by 0.33,0.42 and 0. 52 fold (P < 0. 05). However, at concentration of 1 000 nmol/L, there was no difference in mRNAs content when compare to control (P >0.05). And it showed a decline at concentration of 10,000 nmol/L (P < 0.05). PCNA protein expression was up-regulated at PQQ concentration of 1-100 nmol/L. At 100 nmol/L, the expression increased by 1.17 fold (P < 0.05); However, at 1,000 nmol/L, there was no difference in PCNA expression when compared to control. And 10,000 nmol/L of PQQ inhibited the expression of PCNA (P < 0.05).

CONCLUSIONSWhen treated with PQQ at concentration of 10-100 nmol/L, the proliferation of Schwann cells increased and the expression of c-fos,c-jun, CREB and PCNA was up-regulated.

Animals ; Cell Proliferation ; drug effects ; Cells, Cultured ; Cyclic AMP Response Element-Binding Protein ; metabolism ; Genes, fos ; Genes, jun ; PQQ Cofactor ; pharmacology ; Proliferating Cell Nuclear Antigen ; metabolism ; Rats ; Rats, Sprague-Dawley ; Schwann Cells ; cytology ; drug effects ; metabolism

OBJECTIVETo explore the potential reporter gene assay for the detection of sodium channel-specific toxins in shellfish as an alternative for screening harmful algal bloom (HAB) toxins, considering the fact that the existing methods including HPLC and bioassay are inappropriate for identifying HAB toxins which poses a serious problem on human health and shellfish industry.

METHODSA reporter plasmid pEGFP-c-fos containing c-fos promoter and EGFP was constructed and transfected into T24 cells using LipofectAMINE 2000. Positive transfectants were screened by G418 to produce a pEGFP-c-fos-T24 cell line. After addition of increasing neurotoxic shellfish poison (NSP) or GTX2,3, primary components of paralytic shellfish poison (PSP), changes in expression of EGFP in the cell line were observed under a laser scanning confocal microscope and quantified with Image-pro Plus software.

RESULTSDose-dependent changes in the intensity of green fluorescence were observed for NSP in a range from 0 to 10 ng/mL and for GTX2,3 from 0 to 16 ng/mL.

CONCLUSIONpEGFP-c-fos-T24 can be applied in detecting HAB toxins, and cell-based assay can be used as an alternative for screening sodium channel-specific HAB toxins.

Animals ; Biological Assay ; Cell Line, Tumor ; Genes, Reporter ; physiology ; Green Fluorescent Proteins ; Harmful Algal Bloom ; physiology ; Humans ; Plasmids ; Proto-Oncogene Proteins c-fos ; genetics ; metabolism ; Shellfish ; analysis ; Sodium Channels ; Toxins, Biological ; chemistry ; toxicity

OBJECTIVETo investigate the effects of transforming growth factor beta (TGF ) on c-fos gene expression in hepatic stellate cells.

METHODSHepatic stellate cells (HSC-T6) were cultured in the medium containing different concentrations of TGF (0.2, 1, and 5 ng/ml), and cells were collected at different time points of incubation (8, 24, 48, and 72 h). The total RNA of the HSCs was isolated and c-fos gene expression level were measured by reverse transcription polymerase chain reaction.

RESULTSc-fos gene expression levels of HSCs cultured in the presence of low (0.2 ng/ml), moderate (1 ng/ml) and high (5 ng/ml) concentrations of TGF for 8, 24, 48 and 72 h were significantly greater than those of control group. The c-fos gene expression levels of HSCs increased gradually with the increment of TGF concentration, and significant differences in c-fos gene expression were found between the 3TGF groups.

CONCLUSIONTGF strongly up-regulates c-fos gene expression in hepatic stellate cells.

Animals ; Cells, Cultured ; Gene Expression ; drug effects ; Genes, fos ; Hepatic Stellate Cells ; drug effects ; Proto-Oncogene Proteins c-fos ; genetics ; metabolism ; Rats ; Transforming Growth Factor beta ; pharmacology

BACKGROUND: Chronic post-ischemia pain (CPIP) model is reported to represent the complex regional pain syndrome type I. The administration of non-specific free radical scavengers reduced mechanical allodynia, but it is not evident which type of free radical is responsible for the development of CPIP. This study was investigated to elucidate the role of superoxide on the development of CPIP and the relationship with the expression of c-fos gene. METHODS: Male Sprague-Dawley rats weighing 290-310 g were housed in one cage with food and water ad libitum. CPIP model was made by placing a tourniquet on the left hindpaw of rats. The tourniquet maintained for 3 hours, then released to allow reperfusion. Thirty minutes before reperfusion, superoxide dismutase (SOD) or normal saline (control group) was injected. Mechanical allodynia and cold allodynia were measured at 1, 3, 5, 7, 14 and 28 days after reperfusion and compared. Also, spinal cord was harvested and the expression of c-fos gene was measured through the real time reverse transcription polymerase chain reaction. RESULTS: Superoxide dismutase reduced mechanical allodynia (1, 3, 5 and 14 day) and cold allodynia (1, 3 and 7 day) compared with control rats in left hindpaw. Expression of c-fos was significantly reduced in the SOD rats at the day 14 and 28 compare to the control rats. CONCLUSIONS: The administration of superoxide dismutase suppressed the allodynia and c-fos gene expression of CPIP model rats and it may be suggested that the superoxide has an important role in the development of CPIP.
Animals ; Cold Temperature ; Free Radical Scavengers ; Genes, fos ; Humans ; Hyperalgesia ; Inositol Phosphates ; Male ; Prostaglandins E ; Rats ; Rats, Sprague-Dawley ; Reperfusion ; Reperfusion Injury ; Reverse Transcription ; Spinal Cord ; Superoxide Dismutase ; Superoxides ; Tourniquets ; Water

Exposure to light can induce photoreceptor cell death and exacerbate retinal degeneration. In this study, mice with genetic knockout of several genes, including rhodopsin kinase (Rhok-/-), arrestin (Sag-/-), transducin (Gnat1-/-), c-Fos (c-Fos-/-) and arrestin/transducin (Sag-/-/Gnat1-/-), were examined. We measured the expression levels of thousands of genes in order to investigate their roles in phototransduction signaling in light-induced retinal degeneration using DNA microarray technology and then further explored the gene network using pathway analysis tools. Several cascades of gene components were induced or inhibited as a result of corresponding gene knockout under specific light conditions. Transducin deletion blocked the apoptotic signaling induced by exposure to low light conditions, and it did not require c-Fos/AP-1. Deletion of c-Fos blocked the apoptotic signaling induced by exposure to high intensity light. In the present study, we identified many gene transcripts that are essential for the initiation of light-induced rod degeneration and proposed several important networks that are involved in pro- and anti-apoptotic signaling. We also demonstrated the different cascades of gene components that participate in apoptotic signaling under specific light conditions.
Animals ; Apoptosis/radiation effects ; G-Protein-Coupled Receptor Kinase 1/genetics ; GTP-Binding Protein alpha Subunits/genetics ; *Gene Expression Profiling ; Genes, fos/genetics ; Light/adverse effects ; Light Signal Transduction/*genetics/physiology/radiation effects ; Mice ; Mice, Knockout ; Oligonucleotide Array Sequence Analysis ; Retina/metabolism/pathology/radiation effects ; Retinal Degeneration/etiology/*genetics/physiopathology ; Transducin/genetics

OBJECTIVETo investigate the changes of proto-oncogene c-fos, c-jun mRNA expression in angiotensin II (Ang II)-induced hypertrophy and effects of tanshinone II A (Tan) in the primary culture of neonatal rat cardiomyocytes.

METHODTwelve neonatal Wistar rats aged one day old of clean grade and both sexes were selected to isolate and culture cardiomyocytes. The cardiomyocytes were divided into: normal control group, Ang II (10(-6) mol x L(-1)) group, Ang II (10(-6) mol x L(-1)) +Tan (10(-8) g x L(-1)) group, Ang II (10(-6) mol x L(-1)) + valsartan (10(-6) mol x L(-1)) group, Tan (10(-8) g x L(-1)) group, valsartan (10(-6) mol x L(-1)) group. The cardiomyocyte size was determined by phase contrast microscope, the rate of protein synthesis in cardiomyocytes was measured by 3H-leucine incorporation. The c-fos, c-jun mRNA expression of cardiomyocytes were assessed using reverse transcription polymerase chain reaction (RT-PCR).

RESULTAng II was added to the culture medium and 30 min later, the c-fos, c-jun mRNA expression of cardiomyocytes increased significantly (P < 0. 01). After Ang II took effect for 24 h, the rate of protein synthesis in Ang II group increased more prominently than that in normal control group (P < 0.01). After Ang II took effect for 7 days, the size of cardiomyocyte in Ang II group increased obviously (P < 0. 05). If tanshinone II or valsartan was added to the culture medium before Ang II, both of them could inhibit the increase of c-fos, c-jun mRNA expression (P < 0.01), cardiomyocyte protein synthesis rate (P < 0.01), and cardiomyocyte size (P < 0.05) induced by Ang II.

CONCLUSIONTanshinone II could ameliorate Ang II-induced cardiomyocytes hypertrophy by inhabiting c-fos, c-jun mRNA expression.

Angiotensin II ; biosynthesis ; pharmacology ; Animals ; Cardiomegaly ; chemically induced ; metabolism ; pathology ; Diterpenes, Abietane ; Gene Expression Regulation ; drug effects ; Genes, fos ; genetics ; Genes, jun ; genetics ; Myocytes, Cardiac ; drug effects ; metabolism ; pathology ; Phenanthrenes ; pharmacology ; Proto-Oncogene Proteins c-fos ; genetics ; Proto-Oncogene Proteins c-jun ; genetics ; RNA, Messenger ; genetics ; metabolism ; Rats ; Rats, Wistar ; Tetrazoles ; pharmacology ; Valine ; analogs & derivatives ; pharmacology ; Valsartan

OBJECTIVE: To characterize the antisense c-fos oligonucleotides that control the expression of immediate-early gene c-fos in retina in order to better understand the mechanism by which antisense c-fos oligonucleotides induced myopia. In this study the signal transduction in the pathway linking visual experience and the regulation of the eye's growth was investigated. METHODS: Thirty-one 3-week guinea pigs were assigned into 3 groups: antisense and sense c-fos oligonucleotides were intravitreally injected every 3 days to the eyes of the experimental guinea pigs at different concentrations; and saline vehicle to control guinea pigs in the same way. The refraction and axial length of the eyes were measured before and after the treatment, and the immediate-early gene c-fos expression in the retina was quantified by immunohistochemistry and RT-PCR. RESULTS: The moderate myopia was induced in high (1 nmol) and low (0.1 nmol) level of antisense c-fos oligonucleotide intravitreous injection (-5.425 D and -5.575 D, respectively) compared with the control ateral eyes. The refraction and axial length of the treated eyes increased, and the expression of immediate-early gene c-fos decreased significantly in the antisense c-fos oligonucleotides intravitreously injected eyes compared with the sense c-fos oligonucleotide intravitreously and saline vehicle injected eyes (P<0.01). The refraction and axial length were of no statistically significant differences among the sense c-fos oligonucleotides-treated eyes and saline-treated eyes and non-treated eyes (P>0.05). CONCLUSION The obvious myopia can be induced by antisense c-fos oligonucleotides in guinea pigs; antisense c-fos oligonucleotides inhibit c-fos expression in the retina. Immediate-early gene c-fos may be a potential factor in the prevention of myopia and plays an important role in the signal transduction of the retina.
Animals ; Genes, Immediate-Early ; genetics ; Guinea Pigs ; Immunohistochemistry ; Microinjections ; Myopia ; chemically induced ; genetics ; physiopathology ; Oligonucleotides, Antisense ; administration & dosage ; genetics ; toxicity ; Proto-Oncogene Proteins c-fos ; biosynthesis ; genetics ; RNA, Messenger ; genetics ; metabolism ; Random Allocation ; Retina ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Signal Transduction ; physiology