• The Journal of the Korean bone and joint tumor society
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• v.15 no.2
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• pp.130-137
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• 2009

Purpose: STAT3 is an oncogene that regulates critical cellular processes, and its constitutive activation has been demonstrated to correlate with biological and clinical features in many types of human malignancy. Materials and Methods: In this study, STAT3 activation was assessed in variable benign and malignant chondroid tumors in bone by immunohistochemistry using a monoclonal antibody specific for $tyrosine^{705}$-phosphorylated STAT3 ($pSTAT3^{tyr705}$). Results: Among conventional chondrosarcomas (n=17), three cases(50%) of grade III chondrosarcomas were pSTAT3-positive. All grade I and II chondrosarcomas were pSTAT3-negative. This pSTAT3 positivity according to the histologic grade was statistically significant (p=0.0432). Two cases(50%) of clear cell chondrosarcomas were pSTAT3-positive. Six cases (50%) among 12 benign chondroid tumors(6 enchondromas, 3 chondroblastomas, and 3 chondromyxoid fibromas) were also $pSTAT3^{tyr705}$-positive. Conclusion: In conclusion, STAT3 activation is associated with higher tumor grade in conventional chondrosarcomas. Our results suggest that STAT3 is activated in a subset of benign and malignant chondroid tumors, and may support the extension of the cancer stem cell hypothesis to include tumors of cartilaginous lineage.

• Parasites, Hosts and Diseases
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• v.47 no.2
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• pp.117-124
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• 2009

Toxoplasma gondii provokes rapid and sustained nuclear translocation of the signal transducer and activator of transcription 6 (STAT6) in HeLa cells. We observed activation of STAT6 as early as 2hr after infection with T. gondii by the nuclear translocation of fluorescence expressed from exogenously transfected pDsRed2-STAT6 plasmid and by the detection of phosphotyrosine-STAT6 in Western blot. STAT6 activation occurred only by infection with live tachyzoites but not by co-culture with killed tachyzoites or soluble T. gondii extracts. STAT6 phosphorylation was inhibited by small interfering RNA of STAT6 (siSTAT6). In view of the fact that STAT6 is a central mediator of IL-4 induced gene expression, activation of STAT6 by T. gondii infection resembles that infected host cells has been stimulated by IL-4 treatment. STAT1 was affected to increase the transcription and expression by the treatment of siSTAT6. STAT6 activation was not affected by any excess SOCS's whereas that with IL-4 was inhibited by SOCS-1 and SOCS-3. T. gondii infection induced Eotaxin-3 gene expression which was reduced by $IFN-{\gamma}$. These results demonstrate that T. gondii exploits host STAT6 to take away various harmful reactions by $IFN-{\gamma}$. This shows, for the first time, IL-4-like action by T. gondii infection modulates microbicidal action by $IFN-{\gamma}$ in infected cells.

• Korean Journal of Veterinary Research
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• v.44 no.2
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• pp.163-169
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• 2004

To elucidate the molecular mechanisms of autoimmune inflammation in the central nervous system, we examined the expression and localization of STAT1, STAT3, STAT4 and STAT6 molecules during experimental autoimmune encephalomyelitis (EAE) by competitive PCR. In the present study, we quantitated IL-4 and IL-12 p40 mRNA by competitive PCR in the CNS during EAE. IL-4 mRNA was found at early and peak stages. On the other hand, the IL-12 p40 mRNA level reached maximal levels at the peak stage and still found at the recovery stage of the disease. We examined the kinetics of STAT mRNA in the CNS during EAE and demonstrated that STAT1 and STAT4 mRNA reached a maximal level at the peak stage of EAE, whereas STAT3 mRNA level increased gradually to the recovery stage. STAT6 mRNA increased rapidly at the early stage followed by gradual decrease till the recovery stage. Taken together, these findings suggest that STAT4 which was probably activated by IL-12 plays a pro-inflammatory role and that STAT3 which was activated throughout the disease course seems to serve as a transducer of anti-inflammatory signals.

• Journal of Animal Reproduction and Biotechnology
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• v.36 no.4
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• pp.189-193
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• 2021

Jak-STAT pathway is required for embryogenesis, female gametogenesis, cytokine-mediated neuroprotection, diabetes, obesity, cancer, stem cell, and various tissues. The noncanonical role of Jak-STAT in mitochondria function was supported by the detection of STAT protein in mitochondria, however, several studies show that STAT protein is detected in the endoplasmic reticulum (ER), and not in mitochondria. STAT protein may alter mitochondria function without entering mitochondria, this involves regulation of fission and fusion proteins to change mitochondria morphology. However, how changes in mitochondria morphology lead to changes in mitochondria metabolism needs further investigation.

• Journal of Life Science
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• v.21 no.1
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• pp.141-145
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• 2011

Actinomycin D is a natural antibiotic that is used in anti-cancer chemotherapy and is known as a transcription inhibitor. Interestingly, actinomycin D induces phosphorylation of signal transducers and activators of transcription 3 (STAT3) in renal cancer Caki cells. In this study, we examined the molecular mechanism of actinomycin D-induced STAT3 phosphorylation. Treatment with actinomycin D induced phosphorylation of STAT3 (Tyr705) in a dose- and time-dependent manner. However, actinomycin D did not induce phosphorylation of STAT3 (Ser727), STAT1 (Tyr701) and STAT1 (Ser727). Moreover, actinomycin D-induced STAT3 phosphorylation was caused by decreased protein and mRNA levels of SOCS3, but not by JAK2 and SHP-1. In addition, other transcription inhibitor (5,6-dichloro-1-b-D-ribofuranosyl benzimidazole; DRB) also induced phosphorylation of STAT3 (Tyr705). Taken together, the present study demonstrates that transcriptional inhibitors (actinomycin D and DRB) induce phosphorylation of STAT3 (Tyr705) in Caki cells by down-regulation of SOCS3.

• Molecules and Cells
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• v.23 no.1
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• pp.94-99
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• 2007

Suppressors of cytokine signaling (SOCS) family members are negative feedback regulators of the Jak/Stat pathway, which is an essential inflammatory signaling pathway. We investigated expression of eight members of the SOCS family in rat astrocytes, using two inflammatory stimulants, PMA and IFN-${\gamma}$. Only a few SOCS genes were induced by both stimulants, and we detected an increase in SOCS5 protein with PMA. PMA activated the Jnk, Erk, p38, and Jak/Stat signal pathways. In addition, it increased the level of activated-Stat3 resulting from tyrosine phosphorylation. A gel-shift assay showed that a protein in nuclear extracts from PMA-treated cells was able to bind to Stat binding elements. These results suggest that activated Stat3 binds to SOCS promoters and leads to their transcriptional induction.

• The Mathematical Education
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• v.50 no.3
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• pp.383-394
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• 2011

This paper analyzes subjects related to Math/Stat and studies teaching effect on subject development connected Math/Stat in software curriculum. Among many subjects related to the software, this paper shows exemplary applications of Math/Stat in the software curriculum. Thereby this opens potential application fields of Math/Stat. This confirms that Math/Stat is not only an essential subject to improve competitiveness but also a strategic element in the field of software. Therefore, by maximizing the academic outcome through the interdisciplinary combination of software and Math/Stat, it is possible to educate more competitive and skilled professionals.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.6
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• pp.2873-2877
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• 2012

Objective: To determine STAT3, P-STAT3, and VEGF-C expression levels in small cell lung cancers (SCLCs), and discuss their role and clinical significance in SCLC development. Method: Immunohistochemical methods were applied to 128 cases of SCLC and 40 cases of adjacent normal tissue. Results: The expression levels of STAT3, P-STAT3, and VEGF-C were higher in SCLC than in normal tissue (P<0.05). Pairwise comparisons showed positive correlations with lymph node metastasis, clinical stage, and tumor size (P<0.05). The expression levels were also related with the overall survival rates. Conclusion: STAT3 and VEGF-C play important roles in the development of SCLC, and might be expected to become new targets for SCLC treatment.

• BMB Reports
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• v.52 no.7
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• pp.415-423
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• 2019

Signal transducer and activator of transcription 3 (STAT3) is a cytoplasmic transcription factor that regulates cell proliferation, differentiation, apoptosis, angiogenesis, inflammation and immune responses. Aberrant STAT3 activation triggers tumor progression through oncogenic gene expression in numerous human cancers, leading to promote tumor malignancy. On the contrary, STAT3 activation in immune cells cause elevation of immunosuppressive factors. Accumulating evidence suggests that the tumor microenvironment closely interacts with the STAT3 signaling pathway. So, targeting STAT3 may improve tumor progression, and anti-cancer immune response. In this review, we summarized the role of STAT3 in cancer and the tumor microenvironment, and present inhibitors of STAT3 signaling cascades.

• Journal of Life Science
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• v.30 no.10
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• pp.867-876
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• 2020

This study investigated the repair of UVB-induced cell damage by magnolol. We performed a drug-repurposing screen, and, in the STAT3 reporter gene assay, magnolol was identified as a suppressor of STAT3 that improves the cell viability of HDF cells. HDF cells treated with IL-6, UVB, and IFNγ showed the highest expression of Jak2 and phosphorylated STAT3 (p-STAT3), and magnolol was able to decrease the expression of Jak2 and p-STAT3 in UVB-induced cells. Moreover, UVB-damaged cell growth increased significantly in correlation with both reactivation and with magnolol in a dose-dependent manner. Compared with AG490 (a Jak2 inhibitor) treatment of UVB-treated HDF cells, cell proliferation increased significantly. We confirmed that AG490 and magnolol reduced TNF-α concentrations, and Western blotting (protein level) showed decreases in Jak2 and p-STAT3 expression in only the magnolol-treated cells. The expression of Jak2, p-STAT3, and SOCS3 also increased only after treatment with magnolol. Cells were treated with magnolol and ML385 (an NRF2 inhibitor), and these secondary metabolites reduced cell proliferation and NRF2 expression. The amount of MMP9 was also increased by cotreatment with magnolol and ML385. Collectively, these results demonstrate the potential of magnolol for repairing cells after UVB-induced damage by regulating the expression of NRF2, SOCS3, Jak2, and STAT3.