Serum CYR61 as a potential biomarker to improve breast cancer diagnostics.

To investigate the role of serum CYR61 as a biomarker for the diagnosis of breast cancer and to analyze the association between serum CYR61 levels and the clinicopathological features in breast cancer patients. Serum CYR61 was measured in breast cancer patients and healthy controls by ELISA. The serum levels of CYR61 in breast cancer patients were higher than those in healthy controls.

A Truncated Granulocyte Colony-stimulating Factor Receptor (G-CSFR) Inhibits Apoptosis Induced by Neutrophil Elastase G185R Mutant: IMPLICATION FOR UNDERSTANDING CSF3R GENE MUTATIONS IN SEVERE CONGENITAL NEUTROPENIA.

Mutations in encoding neutrophil elastase (NE) have been identified in the majority of patients with severe congenital neutropenia (SCN). The NE mutants have been shown to activate unfolded protein response and induce premature apoptosis in myeloid cells. Patients with SCN are predisposed to acute myeloid leukemia (AML), and progression from SCN to AML is accompanied by mutations in encoding the granulocyte colony-stimulating factor receptor (G-CSFR) in ∼80% of patients.

Role of Erk1/2 signaling in the regulation of neutrophil versus monocyte development in response to G-CSF and M-CSF.

Lineage specification in the hematopoietic system depends on the expression of lineage specific transcription factors. However, the role of hematopoietic cytokines in this process has been controversial and little is known about the intracellular signaling mechanisms by which cytokines instruct lineage choice. G-CSF and M-CSF are two lineage-specific cytokines that play a dominant role in granulopoiesis and monopoiesis, respectively.

GFI1 is repressed by p53 and inhibits DNA damage-induced apoptosis.

GFI1 is a transcriptional repressor that plays a critical role in hematopoiesis and has also been implicated in lymphomagenesis. It is still poorly understood how GFI1 expression is regulated in the hematopoietic system. We show here that GFI1 transcription was repressed by the tumor suppressor p53 in hematopoietic cells.

Gfi-1 represses CDKN2B encoding p15INK4B through interaction with Miz-1.

Gfi-1 is a nuclear zinc finger (ZF) transcriptional repressor that plays an important role in hematopoiesis and inner ear development, and has been implicated in lymphomagenesis. Gfi-1 represses transcription by directly binding to the consensus DNA sequence in the promoters of its target genes. We report here an alternative mechanism by which Gfi-1 represses CDKN2B encoding p15(INK4B).

Increased CCAAT enhancer-binding protein epsilon (C/EBPepsilon) expression and premature apoptosis in myeloid cells expressing Gfi-1 N382S mutant associated with severe congenital neutropenia.

Granulocyte-colony-stimulating factor (G-CSF) stimulates the activation of multiple signaling pathways, leading to alterations in the activities of transcription factors. Gfi-1 is a zinc finger transcriptional repressor that is required for granulopoiesis. How Gfi-1 acts in myeloid cells is poorly understood.

Involvement of protein kinase Cepsilon in the negative regulation of Akt activation stimulated by granulocyte colony-stimulating factor.

Stimulation of cells with G-CSF activates multiple signaling cascades, including the serine/threonine kinase Akt pathway. We show in this study that G-CSF-induced activation of Akt in myeloid 32D was specifically inhibited by treatment with PMA, a protein kinase C (PKC) activator. PMA treatment also rapidly attenuated sustained Akt activation mediated by a carboxy truncated G-CSF receptor, expressed in patients with acute myeloid leukemia evolving from severe congenital neutropenia.

The G-CSF receptor carboxyl terminus, truncated in AML/SCN, is required for induction of a Stat5 protease activity.

Granulocyte colony-stimulating factor (G-CSF) has been shown to stimulate the activation of the signal transducer and activator of transcription 5 (Stat5). We show here that G-CSF-stimulated activation of Stat5 was attenuated when myeloid cells were induced to differentiate with G-CSF. Attenuated activation of Stat5 correlated with reduced Stat5 protein levels, which was associated with upregulation of a Stat5 protease activity.

Tyrosine 729 of the G-CSF receptor controls the duration of receptor signaling: involvement of SOCS3 and SOCS1.

Mutations in the granulocyte-colony stimulating factor receptor (G-CSF-R) gene resulting in carboxy terminal truncation have been associated with acute myeloid leukemia (AML). The truncated G-CSF-R from AML patients mediate enhanced and prolonged activation of signal transducer and activator of transcription 5 (Stat5). It has been shown that Src homology-2 (SH2)-containing tyrosine phosphatase-1 attenuates the intensity of G-CSF-induced Stat5 activation through interacting with the carboxy terminus of the G-CSF-R.

Fas ligand gene transfer to the embryonic heart induces programmed cell death and outflow tract defects.

The remodeling of the embryonic avian cardiac outflow tract (OFT) involves the removal of cardiomyocytes by programmed cell death (PCD). In contrast, the prevalence of PCD is low in the atrial or ventricular myocytes during this period of development. To determine if this selective PCD is due to the unique ability of the OFT cardiomyocytes to execute PCD, we transduced the embryonic chicken heart in ovo with recombinant adenovirus expressing a death (FasL) ligand.