• The Korean Journal of Pain
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• 제14권2호
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• pp.142-149
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• 2001

Background: The expression of the proto-oncogene c-fos in spinal cord neurons following various noxious stimuli has been demonstrated in numerous studies. However, the pattern of expression of c-fos after incisional stimulus has not been evaluated. This study was designed to examine c-fos expression in an incisional pain model of rats. Methods: A 1 cm longitudinal incision was made through the skin, fascia and muscle of the plantar aspect of the hindpaw in enflurane-anesthetized rats. Withdrawal responses were measured using von Frey filaments at areas around the wound before surgery and for the next 48 hours. The expression of c-fos protein in the lumbar spinal cord was examined by immunohistochemistry. Results: After incision, c-fos was strongly expressed within laminae I, II, III, IV, V and VI ipsilateral to the incision. C-fos positive neurons were detected in the controlateral site, as well. Conclusions: These studies suggest that spinal c-fos protein may not be used as a specific marker for spinal nociceptive processing in an incisional pain model.

• Journal of Magnetics
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• 제20권4호
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• pp.377-380
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• 2015

Muscle contusion has a negative effect on muscle function. Although several studies showed that pain control and muscle recovery is facilitated by pulsed electromagnetic fields (PEMF), there has not been much research regarding the specific effects of PEMF on them. The aim of the present study is to investigate effects of PEMF on pain and muscle recovery following extensor digitorum longus (EDL) contusion injury through measuring the expression of the c-fos proto-oncogene and nerve growth factor (NGF). Significantly reduced c-fos expression in the spinal cord was shown in PEMF groups compared with control (CON) groups. There was no significant difference between PEMF1 and CON1, but significantly increased NGF expression was shown in PEMF3 and PEMF5 compared with in CON groups, where the numbers in the group names are the days from contusion. In conclusion, PEMF could be used to not only reduce pain in muscle injuries by down-regulating c-fos expression in the spinal cord, but it could also influence muscle healing through increasing NGF expression in the injured muscle.

• Molecules and Cells
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• 제20권2호
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• pp.157-166
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• 2005

The c-myc proto-oncogene encodes a nuclear protein that is deregulated and/or mutated in most human cancers. Acting primarily as an activator and sometimes as a repressor, MYC protein controls the synthesis of up to 10-15% of genes. The key MYC targets contributing to oncogenesis are incompletely enumerated and it is not known whether pathology arises from the expression of physiologic targets at abnormal levels or from the pathologic response of new target genes that are not normally regulated by MYC. Regardless of which, available evidence indicates that the level of MYC expression is an important determinant of MYC biology. The c-myc promoter has architectural and functional features that contribute to uniform expression and help to prevent or mitigate conditions that might otherwise create noisy expression. Those features include the use of an expanded proximal promoter, the averaging of input from dozens of transcription factors, and real-time feedback using the supercoil-deformable Far UpStream Element (FUSE) as physical sensor of ongoing transcriptional activity, and the FUSE binding protein (FBP) as well as the FBP interacting repressor (FIR) as effectors to enforce normal transcription from the c-myc promoter.

• BMB Reports
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• 제38권4호
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• pp.500-506
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• 2005

HOX11 encodes a homeodomain-containing transcription factor which directs the development of the spleen during embryogenesis. While HOX11 expression is normally silenced through an unknown mechanism in all tissues by adulthood, the deregulation of HOX11 expression is associated with leukemia, such as T-cell acute lymphoblastic leukemia. The elucidation of regulatory elements contributing to the molecular mechanism underlying the regulation of HOX11 gene expression is of great importance. Previous reports of HOX11 regulatory elements mainly focused on the 5'-flanking region of HOX11 on the chromosome related to transcriptional control. To expand the search of putative cis-elements involved in HOX11 regulation at the post-transcriptional level, we analyzed HOX11 mRNA 3'-untranslated region (3'UTR) and found an AU-rich region. To characterize this AU-rich region, in vitro analysis of HOX11 mRNA 3'UTR was performed with human RNA-binding protein HuR, which interacts with AU-rich element (ARE) existing in the 3'UTR of many growth factors' and cytokines' mRNAs. Our results showed that the HOX11 mRNA 3'UTR can specifically bind with human HuR protein in vitro. This specific binding could be competed effectively by typical ARE containing RNA. After the deletion of the AU-rich region present in the HOX11 mRNA 3'UTR, the interaction of HOX11 mRNA 3'UTR with HuR protein was abolished. These findings suggest that HOX11 mRNA 3'UTR contains cis-acting element which shares similarity in the action pattern with RE-HuR interactions and may involve in the post-transcriptional regulation of the HOX11 gene.

• Journal of Microbiology
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• 제34권2호
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• pp.158-165
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• 1996

The signal transduction pathways through the RAS gene product and adenyl cyclease play a critical role in regulation of the cell cycle in yeast, Saccharomyces cerevisiae. We examined the genetic relationship between the spt3 gene and ras/cAMP pathway. A mutation in the SPT3 gene suppressed cell cycle arrest at the G1 phase caused by either an inactivation of the RAS or CYR1 gene which encodes a yeast homologue of human ras proto-oncogene or adenyl cyclase, respectively. The phenotypes such as sporulation and heat shock resistancy, that resulted from a partial inactivation of the RAS or CYR1 genes, were also suppressed by the spt3 mutation. Expression of the SSA1 gene encoding one of th heat shock proteins (Hsp70) can be induced by heat shock or nitrogen starvation. Expression of this gene is derepressed in cry1-2 and spt3 mutants. The bcy 1 mutation repressed by the bcy1 mutation, but not in spt3 mutants. These results suggest that the SPT gene is involved in expression of genes that are affected by the RAS/cAMP pathway.

• Journal of Life Science
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• 제9권2호
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• pp.52-56
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• 1999

The Raf, a cytoplasmic serine/thereonine protein kinase, acts as an important mediator of signals involving cell proliferation, differentiation and development. Multiple regulatory elements should participate in the expression of D-raf, Drosophila homolog of human c-raf-1. In order to search regulatory factors involved in the D-raf promoter activation, we accomplished the yeast one-hybrid screening using D-raf promoter region from bp-330 to -309 with respect to the transcription initiation site as bait. After screening, sixteen independent positive clones of ${\beta}$-galactosidase activties were identified and sequenced. Two clones having 94-98% identity with daughterless and one clone having 93% identity with escargot by Blast search among these clones were screened.

• Asian Pacific Journal of Cancer Prevention
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• 제14권1호
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• pp.15-20
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• 2013

Urinary bladder squamous cell carcinoma (SCC), one of the most common neoplasms in Egypt, is attributed to chronic urinary infection with Schistosoma haematobium (Schistosomiasis). The proto-oncogene c-KIT, encoding a tyrosine kinase receptor and implicated in the development of a number of human malignancies, has not been studied so far in schistosomal urinary bladder SCCs. We therefore determined immunohistochemical (IHC) expression of c-KIT in paraffin sections from 120 radical cystectomies of SCCs originally obtained from the Pathology Department of Suez Canal University (Ismailia, Egypt). Each slide was evaluated for staining intensity where the staining extent of >10% of cells was considered positive. c-KIT overexpression was detected in 78.3% (94/120) of the patients, the staining extents in the tumor cells were 11-50% and >50% in 40 (42.6%) and 54 (57.4%) respectively. The positive cases had 14.9%, 63.8%, 21.3% as weak, moderate and strong intensity respectively. Patients with positive bilharzial ova had significantly higher c-KIT expression than patients without (95.2% vs. 38.9%, P=0.000). Mutation analysis of exons 9-13 was negative in thirty KIT positive cases. The high rate of positivity in SBSCC was one of the striking findings; However, CD117 may be a potential target for site specific immunotherapy to improve the outcome of this tumor.

• Journal of Animal Science and Technology
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• 제62권3호
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• pp.385-395
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• 2020

Polyinosinic:polycytidylic acid (poly[I:C]) can stimulate Toll-like receptor 3 (TLR3) signaling pathways. In this study, DF-1 cells were treated with poly(I:C) at various concentrations and time points to examine the comparative expression patterns of innate immune response genes. The viability of DF-1 cells decreased from 77.41% to 38.68% when cells were treated different dose of poly(I:C) from 0.1 ㎍/mL to 100 ㎍/mL for 24 h respectively. The expressions of TLR3, TLR4, TLR7, TLR15, TLR21, IL1B, and IL10 were increased in dose- and time-dependent manners by poly(I:C) treatment. On the contrary, the expression patterns of interferon regulatory factors 7 (IRF7), Jun proto-oncogene, AP-1 transcription factor subunit (JUN), Nuclear Factor Kappa B Subunit 1 (NF-κB1), and IL8L2 were varied; IRF7 and IL8L2 were increasingly expressed whereas the expressions of JUN and NF-κB1 were decreased in a dose-dependent manner after they were early induced. In time-dependent analysis, IRF7 expression was significantly upregulated from 3 h to 24 h, whereas JUN and NF-κB1 expressions settled down from 6 h to 24 h after poly(I:C) treatment although they were induced at early time from 1 h to 3 h. Poly(I:C) treatment rapidly increased the expression of IL8L2 from 3 h to 6 h with a plateau at 6 h and then the expression of IL8L2 was dramatically decreased until 24 h after poly(I:C) treatment although the expression level was still higher than the non-treated control. These results may provide the basis for understanding host response to viral infection and its mimicry system in chickens.

• Animal cells and systems
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• 제1권1호
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• pp.151-155
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• 1997

Promoter of the Drosophila proliferating cell nuclear antigen (PCNA) gene contains DRE (Drosophila DNA replication-related element) required for the high level expression of replication-related genes. Recently, we found that promoter region of the D-raf (a Drosophila homolog of the human c-raf-1) contains two sequences homologous to the DRE and demonstrated the DRE/DREF (DRE-binding factor) involvement in regulation of the D-raf gene. In this study, using ursolic acid (UA), a pentacyclic triterpene acid reported to possess antitumor activities, we examined effects of UA on proliferation of the Drosophila cultured Kc cells and on expression of the PCNA and D-raf genes. UA showed an inhibitory effect on proliferation of the Kc cells in a concentration-dependent manner in DNA content assays and [3H]thymidine incorporation assays. The IC50 value of anti-proliferative effects of UA in DNA content assays was about 7.5uM. UA showed inhibitory effects on expression of the PCNA as well as on that of the D-raf, which were examined with the reporter plasmic p5'-168DPCNACAT or p5'-878DrafCAT, respectively. The results obtained in the present study suggest that expression of the PCNA and D-raf genes is coordinately regulated in at least UA-treated Kc cells and that down-regulation of expression of the PCNA and D-raf genes might be related with the antitumor activities of UA.

• The Korean Journal of Physiology and Pharmacology
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• 제27권4호
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• pp.383-398
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• 2023

Dihydroaustrasulfone alcohol (DA), the synthetic precursor of a natural compound (austrasulfone) isolated from the coral species Cladiella australis, has shown cytotoxic effects against cancer cells. However, it is unknown whether DA has antitumor effects on nasopharyngeal carcinoma (NPC). In this study, we determined the antitumor effects of DA and investigated its mechanism of action on human NPC cells. The MTT assay was used to determine the cytotoxic effect of DA. Subsequently, apoptosis and reactive oxygen species (ROS) analyses were performed by using flow cytometry. Apoptotic and PI3K/AKT pathway-related protein expression was determined using Western blotting. We found that DA significantly reduced the viability of NPC-39 cells and determined that apoptosis was involved in DA-induced cell death. The activity of caspase-9, caspase-8, caspase-3, and PARP induced by DA suggested caspase-mediated apoptosis in DA-treated NPC-39 cells. Apoptosis-associated proteins (DR4, DR5, FAS) in extrinsic pathways were also elevated by DA. The enhanced expression of proapoptotic Bax and decreased expression of antiapoptotic BCL-2 suggested that DA mediated mitochondrial apoptosis. DA reduced the expression of pPI3K and p-AKT in NPC-39 cells. DA also reduced apoptosis after introducing an active AKT cDNA, indicating that DA could block the PI3K/AKT pathway from being activated. DA increased intracellular ROS, but N-acetylcysteine (NAC), a ROS scavenger, reduced DA-induced cytotoxicity. NAC also reversed the chances in pPI3K/AKT expression and reduced DA-induced apoptosis. These findings suggest that ROS-mediates DA-induced apoptosis and PI3K/AKT signaling inactivation in human NPC cells.