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STAT3 Expression (stat3 + expression)
Selected AbstractsHsp105, upregulates hsp70 gene expression through signal transducer and activator of transcription-3FEBS JOURNAL, Issue 20 2009Nobuyuki Yamagishi Hsp105, and Hsp105, are mammalian members of the Hsp105/110 family, a divergent subgroup of the Hsp70 family. Hsp105, is expressed constitutively and induced by various forms of stress, whereas Hsp105, is an alternatively spliced form of Hsp105, that is expressed specifically during mild heat shock. In a report, it was shown that Hsp105, and Hsp105, localize to the cytoplasm and of nucleus of cells, respectively, and that Hsp105,, but not Hsp105,, induces the expression of Hsp70 in mammalian cells. Here, we examined the mechanism by which Hsp105, induces the expression of Hsp70. Using a series of deletion mutants of Hsp105,, it was revealed that the region between amino acids 642 and 662 of Hsp105, is necessary for the activation of the hsp70 promoter by Hsp105,. Furthermore, it was shown that signal transducer and activator of transcription (STAT)-3 bound to the sequence of the hsp70 promoter between ,206 and ,187 bp, and that mutations of this sequence abrogated the activation of the hsp70 promoter by Hsp105,. In addition, overexpression of Hsp105, stimulated the phosphorylation of STAT3 at Tyr705 and its translocation to the nucleus. Downregulation of STAT3 expression resulted in reduction of the activation of the hsp70 promoter by Hsp105,. Furthermore, downregulation of Hsp105, reduced the expression of Hsp70 in heat-shocked cells. On the basis of these findings, it is suggested that Hsp105, induces Hsp70 expression markedly through the STAT3 pathway in heat-shocked cells. This may represent the mechanism that connects the heat shock protein and STAT families for cell defense against deleterious stress. [source] STAT3 expression in gastric cancer indicates a poor prognosisJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 4 2009Dae-Young Kim Abstract Background and Aim:, Signal transducers and activators of transcription (STAT) behave as signal transducers in the cytoplasm and as transcription factors in the nucleus. In the current study, we analyzed the immunohistochemical staining patterns of gastrectomy tissue specimens. We investigated the expression of STAT3 and STAT5 and estimated the relationship between STAT and cancer prognosis. Methods:, One hundred patients who underwent gastrectomy due to gastric adenocarcinoma at Bundang CHA hospital between January 2000 and May 2005 were studied. Immunohistochemistry was carried out using antibodies against STAT3 and STAT5. The interpretation of the immunohistochemical staining was based on the proportion of stained cells in the field: positive, > 10% stained cells; and negative, < 10% stained cells. Results:, The longest diameter of tumor was 4.67 cm in the positive group and 3.76 cm in the negative group, and these results were not statistically different (P -value = 0.112). Higher T (primary tumor) value (P -value = 0.05), more regional lymph node invasion (P -value = 0.008) and higher TNM staging (P -value = 0.069) were significantly related to STAT3 positivity, but Helicobacter pylori infection or atrophic gastritis were not related. A lower survival rate was observed in the STAT3-positive group (P -value = 0.001). The results of STAT5 were not statistically different with respect to TNM staging and survival (P -value = 0.958). We thus report that the immunohistochemical results of STAT3 revealed a significant association with TNM staging and survival. Conclusion:, We anticipate that STAT3 may be used as a molecular staging biomarker predicting poor prognosis of gastric cancer. [source] 1141638491 Hepatocyte growth factor (HGF) stimulates mammalian target of rapamycin (mTOR) in choriocarcinoma cell lines and human trophoblast cellsAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 6 2006S Busch Introduction:, Hepatocyte growth factor (HGF), interleukin-6 (IL-6) and insulin-like growth factor-II (IGF-II) are involved in the regulation of trophoblast cell migration and invasion. Signal Transducer and Activator of Transcription 3 (STAT3) and Mammalian Target Of Rapamycin (mTOR) signalling regulate cell invasion, growth and proliferation. mTOR plays also a key role during embryogenesis. Knock-out mice embryos die after implantation and blastocysts trophoblast outgrowth is reduced. Aim:, Stimuli which might trigger such invasive behaviour through mTOR should be defined. Methods:, The human choriocarcinoma cell lines JEG-3, JAR, the human choriocarcinoma-trophoblast hybrid AC1-M59 and human term trophoblast cells were stimulated with HGF, IL-6 or IGF-II. At several time points, the phosphorylation level of mTOR and STAT3 were tested by Western blot. STAT3 DNA-binding capacity was analyzed by Electrophorectic Mobility Shift Assay (EMSA). To examine the role of mTOR for invasion and proliferation, mTOR expression was silenced by RNA interference (RNAi). Results:, HGF, IGF-II and IL-6 did neither induce tyrosine (705) phosphorylation of STAT3 nor STAT3 DNA binding capacity as assessed by EMSA. HGF led to an increase of mTOR serine (2448) phosphorylation for all cell types after 15 and 30 min while IL-6 and IGF-II did not induce mTOR phosphorylation. Simultaneously, HGF decreased STAT3 serine (727) phosphorylation. mTOR silencing in AC1-M59 correlates with reduced proliferation and invasion. STAT3 expression was not affected by mTOR knock down. Conclusion:, HGF triggers mTOR activity in trophoblast and trophoblast-like cells. mTOR is a main regulator of crucial trophoblast functions. [source] Activated Stat3 expression in gestational trophoblastic disease: correlation with clinicopathological parameters and apoptotic indicesHISTOPATHOLOGY, Issue 2 2008H Y Chan Aims:, To assess the expression profile of the activated form of signal transducer and activator of transcription (Stat)3 in gestational trophoblastic disease (GTD) and correlate the findings with clinicopathological parameters. Methods and results:, By immunohistochemistry, both cytoplasmic and nuclear expression of p-Stat3-Ser727 was demonstrated in 88 trophoblastic tissues, including placentas and GTD. Nuclear immunoreactivity of p-Stat3-Ser727 was significantly higher in hydatidiform mole (HM) (P < 0.001) and choriocarcinoma (P = 0.009) when compared with normal placentas. Placental site trophoblastic tumours (PSTT) and epithelioid trophoblastic tumours (ETT) also demonstrated higher nuclear p-Stat3-Ser727 expression than their normal trophoblast counterparts. Higher p-Stat3-Ser727 expression was confirmed in choriocarcinoma cell lines, JEG-3 and JAR, than in a normal trophoblast cell line, with both nuclear and cytoplasmic fractions demonstrated by immunoblotting. Spontaneously regressed HM showed significantly increased nuclear and cytoplasmic p-Stat3-Ser727 immunoreactivity over those that developed gestational trophoblastic neoplasia (GTN) (P = 0.013, P = 0.039). There was a significant positive and inverse correlation between nuclear p-Stat3-Ser727 immunoreactivity and apoptotic indices [terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP) nick end labelling and M30 CytoDeath antibody] (P = 0.001, P < 0.001, Spearman's , test) and Bcl-2 expression (P = 0.034), respectively. Conclusions:, p-Stat3-Ser727 plays a role in the pathogenesis of GTD, probably through the regulation of apoptosis. p-Stat3-Ser727 immunoreactivity is a potential marker in predicting GTN in HM. [source] A link between the interleukin-6/Stat3 anti-apoptotic pathway and microRNA-21 in preimplantation mouse embryosMOLECULAR REPRODUCTION & DEVELOPMENT, Issue 9 2009Xing-Hui Shen Signal transducers and activators of transcription-3 (Stat3) plays a central role in interleukin-6 (IL-6)-mediated cell proliferation by inhibiting apoptosis in a variety of cell types. MicroRNA-21 (miRNA-21), a ubiquitous miRNA, acts as an anti-apoptotic factor that seems to be indirectly but strictly linked to Stat3. In order to determine whether the IL-6 induced Stat3 anti-apoptosis pathway is linked with miRNA-21, we first determined the effects of recombinant mouse IL-6 on Stat3 expression, mouse embryo viability, and the mRNA levels of apoptosis related genes and miRNA-21 during mouse embryo development in vitro. Addition of 10 or 100,ng/ml of recombinant IL-6 to the culture medium did not affect the developmental ability of 2-cell stage embryos into blastocysts. However, total cell number was significantly increased and apoptosis was reduced in blastocyst stage embryos cultured in the presence of 100,ng/ml of recombinant IL-6. Furthermore, addition of recombinant IL-6 to the culture medium significantly increased the copy numbers of anti-apoptotic miRNA-21, up-regulated Bcl2l1, and down-regulated casp3. Similarly, the injection of mature miRNA-21 into cells up-regulated Bcl2l1 and down-regulated casp3. These results suggest that the induction of the Stat3 anti-apoptotic pathway by IL-6 is linked to miRNA-21 expression, which possibly results in the regulation of cell apoptosis in early mouse embryo development. Mol. Reprod. Dev. 76: 854,862, 2009. © 2009 Wiley-Liss, Inc. [source] Differential expression and activation of Stat3 during mouse embryo implantation and decidualizationMOLECULAR REPRODUCTION & DEVELOPMENT, Issue 1 2004Chun-Bo Teng Abstract Signal transducer and activator of transcription (STATs) can be activated by many cytokines and growth factors. Stat3, a member of STAT family, is essential for embryonic development. Stat3 is specifically activated during mouse embryo implantation. This study was to investigate the expression, activation, and regulation of Stat3 in mouse uterus during early pregnancy, pseudopregnancy, delayed implantation, artificial decidualization, and hormonal treatments using in situ hybridization and immunohistochemistry. There was a strong level of Stat3 phosphorylation in the luminal epithelium only at the midnight of day 4 pregnancy, which coincides with attachment reaction between the blastocyst and luminal epithelium. However, there was no detectable Stat3 phosphorylation at the corresponding period during pseudopregnancy. On day 5 of pregnancy, Stat3 phosphorylation was strongly observed in the luminal epithelium and the stroma surrounding the implanting blastocyst at implantation sites, but not at the inter-implantation sites. Stat3 phosphorylation was also not detected on day 5 of pseudopregnancy. Stat3 phosphorylation was at a high level in the decidual cells on days 6,8 of pregnancy. Under artificial decidualization, Stat3 was also phosphorylated in the decidual cells. In the ovariectomized mice, there was no Stat3 expression and activation in the uterus. Progesterone had no obvious effects. However, Stat3 mRNA expression and phosphorylation were significantly stimulated by estrogen treatment. Our data suggest that Stat3 phosphorylation may be important for mouse embryo implantation and decidualization, and may also be regulated by maternal estrogen. Mol. Reprod. Dev. 69: 1,10, 2004. © Wiley-Liss, Inc. [source] | ||||||||||