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STAT5 Phosphorylation (stat5 + phosphorylation)

Distribution by Scientific Domains

Medical Sciences	100%

Selected Abstracts

Reduced numbers of IL-7 receptor (CD127) expressing immune cells and IL-7-signaling defects in peripheral blood from patients with breast cancer

INTERNATIONAL JOURNAL OF CANCER, Issue 7 2007
Nalini Kumar Vudattu
Abstract Interleukin-7-receptor-signaling plays a pivotal role in T-cell development and maintenance of T-cell memory. We studied IL-7R, (CD127) expression in PBMCs obtained from patients with breast cancer and examined IL-7 receptor-mediated downstream effects defined by STAT5 phosphorylation (p-STAT5). Reduced numbers of IL-7R,-positive cells were identified in CD4+ T-cells as well as in a CD8+ T-cell subset defined by CD8,/, homodimer expression in patients with breast cancer. PBMCs obtained from healthy donors (n = 19) and from patients with breast cancer (n = 19) exhibited constitutive p-STAT5 expression in the range of 0,6.4% in CD4+ T-cells and 0,4% in CD8+ T-cells. Stimulation with recombinant human IL-7 for 15 min increased p-STAT5 expression up to 36,97% in CD4+T-cells and to 26,90% in CD8+T-cells obtained from healthy control donors (n = 19). In contrast, PBMCs obtained from 13/19 patients with breast cancer did not respond to IL-7 as defined by STAT5 phosphorylation, despite expression of IL-7R, on T-lymphocytes. T-cells were further characterized for IL- 2 and IFN-, production induced by PMA/Ionomycin. PBMCs from 9/19 patients with breast cancer showed decreased IL-2 and IFN-, production combined with IL-7-signaling defects; PBMCs from 4 patients with breast cancer exhibited deficient IL-7-signaling, yet intact cytokine production. Reduced numbers of IL-7R,-positive cells and nonresponsiveness to IL-7, defined by lack of STAT5 phosphorylation, characterizes the immunological profile in T-cells from patients with breast cancer. © 2007 Wiley-Liss, Inc. [source]

FAK silencing inhibits leukemogenesis in BCR/ABL-transformed hematopoietic cells,

AMERICAN JOURNAL OF HEMATOLOGY, Issue 5 2009
Yi Le
Focal adhesion kinase (FAK) is constitutively activated and tyrosine phosphorylated in BCR/ABL-transformed hematopoietic cells, but the role it plays during leukemogenesis remains unclear. Here, we examined the effects of RNA interference-mediated FAK silencing on leukemogenesis induced by a BCR/ABL-transformed cell line. Transduction of BCR/ABL-BaF3 cells with FAK shRNA inhibited FAK expression and reduced STAT5 phosphorylation, but induced caspase-3 activation. In vitro studies showed that treatment with FAK shRNA resulted in impaired cell proliferation and colony formation, while increasing cell apoptosis. Mice that received transplants of BCR/ABL-BaF3 cells with FAK shRNA displayed significantly prolonged survival time and diminished leukemia progression. In addition, FAK silencing enhanced in vitro and in vivo efficacy of ABL tyrosine kinase inhibitor imatinib in BCR/ABL-BaF3 cells. Our results suggest that FAK is critical for leukemogenesis and might be a potential target for leukemia therapy. Am. J. Hematol. 2009. © 2009 Wiley-Liss, Inc. [source]

Erythropoietin stimulates growth and STAT5 phosphorylation in human prostate epithelial and prostate cancer cells

THE PROSTATE, Issue 2 2006
Laurie Feldman
Abstract BACKGROUND Erythropoietin (Epo), the principal regulator of erythroid progenitor survival, growth, and differentiation, initiates its action by binding to its cognate cell surface receptor (EpoR). EpoR have been identified on a variety of non-hematopoietic cells, both normal and malignant, however, little is known about the function of EpoR on malignant cells. METHODS RT-PCR, Western blotting, and immunohistochemistry were used to demonstrate that prostate cancer cells express EpoR at both the gene and protein level. Cell proliferation assays and STAT5 phosphorylation were used to demonstrate Epo's mitogenic action and intracellular signaling, respectively. RESULTS We have demonstrated that transformed prostate epithelial and prostate cancer cell lines, as well as primary prostate tissue, express the EpoR. Importantly, the EpoR on prostate cells are functional, as demonstrated by the observation that each of the cell lines exhibited a dose-dependent proliferative response to Epo, and that Epo triggered STAT5b phosphorylation in the cells. CONCLUSION Human prostatic epithelial cells and prostate cancer cells express functional EpoR, and Epo serves as a growth factor for these cells. These results have implications for our understanding of normal prostatic growth and development and of the pathobiology of human prostate cancer. © 2005 Wiley-Liss, Inc. [source]

Early growth response 2 regulates the survival of thymocytes during positive selection

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 1 2010
Victoria J. Lawson
Abstract The early growth response (Egr) transcription factor family regulates multiple steps during T-cell development. We examine here the role played by Egr2 in positive selection. In double-positive cells, Egr2 is upregulated immediately following TCR ligation, and its expression requires both the MAPK and calcineurin signaling pathways. Inducible transgenic and knockout mice were generated to cause gain- or loss-of-function of Egr2 in double-positive cells, and had reciprocal effects; more mature single-positive cells were made when Egr2 was overexpressed, and fewer when Egr2 was absent. These defects were associated with changes in the survival of positively selected cells rather than perturbation of positive selection or immediate post-selection signaling. The survival function of Egr2 at least partly depends upon its ability to activate the cytokine-mediated survival pathway, likely through negative regulation of both the IL-7R and suppressor of cytokine signaling 1 (Socs1), the molecular switch whose downregulation normally results in restored responsiveness to cytokine signaling following selection. While gain of Egr2 caused a decrease in Socs1 mRNA, loss of Egr2 resulted in downregulation of IL-7R, upregulation of Socs1, and inhibition of Stat5 phosphorylation and IL-7-mediated survival post-selection. Therefore, expression of Egr2 following positive selection links the initial TCR signaling event to subsequent survival of signaled cells. [source]