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STAT3 Pathways (stat3 + pathway)

Distribution by Scientific Domains

Medical Sciences	75%

Selected Abstracts

Hsp105, upregulates hsp70 gene expression through signal transducer and activator of transcription-3

FEBS JOURNAL, Issue 20 2009
Nobuyuki 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]

Concordant overexpression of phosphorylated ATF2 and STAT3 in extramammary Paget's disease

JOURNAL OF CUTANEOUS PATHOLOGY, Issue 4 2009
Si-Yuan Chen
Background:, Activating transcription factor 2 (ATF2) and signal transducer and activator of transcription 3 (STAT3) play important roles in the pathogenesis of various tumors, but ATF2 expression/activation and the relationship with STAT3 activation have not yet been investigated in extramammary Paget's disease (EMPD). Objective:, To investigate potential contributions of ATF2 and STAT3 pathways to the pathogenesis of EMPD. Method:, Paraffin-embedded 45 EMPD specimens (43 primary EMPD and 2 nodal metastases) were subjected to immunohistochemical staining for ATF2, phosphorylated (p)-ATF2 and p-STAT3. Results:, P-ATF2 expression in advanced EMPD, non-invasive EMPD and normal skin (NS) controls were 97.9 ± 1.8%, 82.0 ± 23.4% and 45.8 ± 3.2%, respectively, and p-STAT3 expression in advanced EMPD, non-invasive EMPD and NS were 97.0 ± 2.9%, 83.2 ± 23.3% and 50.1 ± 6.7%, respectively. P-ATF2 and p-STAT3 expressions in EMPD were significantly higher than those in NS, indicating a possible contribution of these pathways to the tumor development. P-ATF2 and p-STAT3 expressions in advanced EMPD were significantly higher than those in non-invasive EMPD, possibly indicating that these pathways might also contribute to the tumor invasion and/or metastasis. We also found an exceptionally high positive correlation between p-ATF2 and p-STAT3 expressions in EMPD. Conclusions:, P-ATF2 and p-STAT3 are concordantly overexpressed in EMPD and their expressions may possibly be associated with the tumor stage. [source]

Genistein-induced neuroendocrine differentiation of prostate cancer cells

THE PROSTATE, Issue 11 2006
Jacek Pinski MD
Abstract BACKGROUND Neuroendocrine (NE) cells are present in normal prostate and their number appears to be increased in advanced prostate cancer (PCA). In this study, we studied the effect of the phytoestrogen, genistein, on NE differentiation of LNCaP cells in vitro. METHODS Neuroendocrine marker expression of LNCaP cells exposed to genistein was measured by immunohistochemistry, Western blot, and real-time PCR methods. Western blot analysis was used to study cell cycle and signaling pathways induced by genistein treatment. RESULTS Six days after continuous genistein treatment, the majority of genistein-surviving cancer cells underwent transdifferentiation into a NE-like phenotype overexpressing the NE markers chromogranin A, synaptophysin, serotonin, and beta-III tubulin. This NE differentiation process was associated with upregulation of the cell cycle modulators p21, p27, and p53, and activation of the MAPK and STAT3 pathways. CONCLUSION Our data indicate that genistein evokes not only apoptosis but also NE transdifferentiation of PCA cells. Prostate © 2006 Wiley-Liss, Inc. [source]

Interleukin-6 protects LNCaP cells from apoptosis induced by androgen deprivation through the Stat3 pathway

THE PROSTATE, Issue 3 2004
Soo Ok Lee
Abstract BACKGROUND Elevated expression of interleukin-6 (IL-6) is implicated in the progression of hormone refractory prostate cancer. Previous studies demonstrated that IL-6 promotes androgen-independent growth of prostate cancer cells. In this study, the effect of IL-6 on apoptosis induced by androgen deprivation was investigated. METHODS The effect of IL-6 on apoptosis induced by androgen deprivation in LNCaP cells was examined by cell death ELISA and Western blot using cleaved poly (ADP-ribose) polymerase (PARP) and caspase-9, as well as Bcl-xL and phosphorylated Bad. The Stat3 in IL-6-mediated anti-apoptosis in prostate cancer cells was examined using either dominant-negative or constitutively activated Stat3 mutants. RESULTS Overexpression of IL-6 renders androgen sensitive LNCaP human prostate cancer cells more resistant to apoptosis induced by androgen deprivation. LNCaP cells undergo apoptosis after 72 hr of androgen deprivation, an outcome is largely absent in clones overexpressing IL-6 as measured by cell death ELISA and chromatin degradation assays. IL-6 over-expressing cells resulted in a significant decrease in the expression of cleaved PARP and cleaved caspase-9 as well as an increase in the expression of Bcl-xL and phosphorylated Bad. Addition of IL-6 antibody completely abolished the anti-apoptotic activity of IL-6. This protective effect of IL-6 was reversed by the expression of a dominant-negative Stat3 mutant, Stat3F. Furthermore, ectopic expression of a constitutively active Stat3 antagonized androgen deprivation-induced cell death of LNCaP cells. CONCLUSION These results indicate that IL-6 protects androgen sensitive LNCaP cells from apoptosis induced by androgen deprivation, and Stat3 activation play an important role in IL-6-mediated anti-apoptosis in prostate cancer cells. © 2004 Wiley-Liss, Inc. [source]