Itraconazole Exerts Its Antitumor Effect in Esophageal Cancer By Suppressing the HER2/AKT Signaling Pathway.

Itraconazole, an FDA-approved antifungal, has antitumor activity against a variety of cancers. We sought to determine the effects of itraconazole on esophageal cancer and elucidate its mechanism of action. Itraconazole inhibited cell proliferation and induced G-phase cell-cycle arrest in esophageal squamous cell carcinoma and adenocarcinoma cell lines.

GEAMP, a novel gastroesophageal junction carcinoma cell line derived from a malignant pleural effusion.

Gastroesophageal junction (GEJ) cancer remains a clinically significant disease in Western countries due to its increasing incidence, which mirrors that of esophageal cancer, and poor prognosis. To develop novel and effective approaches for prevention, early detection, and treatment of patients with GEJ cancer, a better understanding of the mechanisms driving pathogenesis and malignant progression of this disease is required. These efforts have been limited by the small number of available cell lines and appropriate preclinical animal models for in vitro and in vivo studies.

Profiling of REST-Dependent microRNAs Reveals Dynamic Modes of Expression.

Multipotent neural stem cells (NSCs) possess the ability to self-renew and differentiate into both neurons and glia. However, the detailed mechanisms underlying NSC fate decisions are not well understood. Recent work suggests that the interaction between cell type specific transcription factors and microRNAs (miRNAs) is important as resident neural stem/progenitor cells give rise to functionally mature neurons.

The master negative regulator REST/NRSF controls adult neurogenesis by restraining the neurogenic program in quiescent stem cells.

Transcriptional regulation is a critical mechanism in the birth, specification, and differentiation of granule neurons in the adult hippocampus. One of the first negative-acting transcriptional regulators implicated in vertebrate development is repressor element 1-silencing transcription/neuron-restrictive silencer factor (REST/NRSF)--thought to regulate hundreds of neuron-specific genes--yet its function in the adult brain remains elusive. Here we report that REST/NRSF is required to maintain the adult neural stem cell (NSC) pool and orchestrate stage-specific differentiation.

Cardiac myosin light chain kinase is necessary for myosin regulatory light chain phosphorylation and cardiac performance in vivo.

In contrast to studies on skeletal and smooth muscles, the identity of kinases in the heart that are important physiologically for direct phosphorylation of myosin regulatory light chain (RLC) is not known. A Ca(2+)/calmodulin-activated myosin light chain kinase is expressed only in cardiac muscle (cMLCK), similar to the tissue-specific expression of skeletal muscle MLCK and in contrast to the ubiquitous expression of smooth muscle MLCK. We have ablated cMLCK expression in male mice to provide insights into its role in RLC phosphorylation in normally contracting myocardium.

Molecular cloning and identification of mouse Cklfsf2a and Cklfsf2b, two homologues of human CKLFSF2.

Human chemokine-like factor superfamily (CKLFSF) is a novel gene family comprising CKLF and CKLFSF1-8. Among them, CKLFSF2 is highly expressed in testis and may play important roles in male reproduction. Besides, it is very active during evolution and has two counterparts in mouse.

Myosin light chain kinase and myosin phosphorylation effect frequency-dependent potentiation of skeletal muscle contraction.

Repetitive stimulation potentiates contractile tension of fast-twitch skeletal muscle. We examined the role of myosin regulatory light chain (RLC) phosphorylation in this physiological response by ablating Ca(2+)/calmodulin-dependent skeletal muscle myosin light chain kinase (MLCK) gene expression. Western blot and quantitative-PCR showed that MLCK is expressed predominantly in fast-twitch skeletal muscle fibers with insignificant amounts in heart and smooth muscle.

Regulation of EGF receptor signaling by the MARVEL domain-containing protein CKLFSF8.

It is known that chemokine-like factor superfamily 8 (CKLFSF8), a member of the CKLF superfamily, has four putative transmembrane regions and a MARVEL domain. Its structure is similar to TM4SF11 (plasmolipin) and widely distributed in normal tissue. However, its function is not yet known.

CKLFSF2 is highly expressed in testis and can be secreted into the seminiferous tubules.

CKLFSF2 is a member of the chemokine-like factor superfamily (CKLFSF), a novel gene family containing CKLF and CKLFSF1-8. Using a combination of data mining and polymerase chain reactions, we determined the full cDNA sequence and genomic structure of human CKLFSF2, a 4-exon gene encoding 248 amino acids and spanning approximately 8.8 kb on chromosome 16q22.

Chemokine-like factor 1, a novel cytokine, contributes to airway damage, remodeling and pulmonary fibrosis.

Background: Chemokine-like factor 1 (CKLF1) was recently identified as a novel cytokine. The full-length CKLF1 cDNA contains 530 bp encoding 99 amino acid residues with a CC motif similar to that of other CC family chemokines. Recombinant CKLF1 exhibits chemotactic activity on leucocytes and stimulates proliferation of murine skeletal muscle cells.

Molecular cloning and characterization of chemokine-like factor super family member 1 (CKLFSF1), a novel human gene with at least 23 alternative splicing isoforms in testis tissue.

Chemokine-like factor (CKLF) was isolated from PHA-stimulated U937 cells. It is composed of 152 amino acids and located on chromosome 16q22. Utilizing bioinformatics, based on CKLF cDNA and protein sequences, in combination with experimental validation, we identified a novel gene designated chemokine-like factor super family member 1 (CKLFSF1).

An alternative form of paraptosis-like cell death, triggered by TAJ/TROY and enhanced by PDCD5 overexpression.

Accumulating reports demonstrate that apoptosis does not explain all the forms of programmed cell death (PCD), particularly in individual development and neurodegenerative disease. Recently, a novel type of PCD, designated 'paraptosis', was described. Here, we show that overexpression of TAJ/TROY, a member of the tumor necrosis factor receptor superfamily, induces non-apoptotic cell death with paraptosis-like morphology in 293T cells.

Last intron of the chemokine-like factor gene contains a putative promoter for the downstream CKLF super family member 1 gene.

The genes for chemokine-like factor (CKLF) and four chemokine-like factor super family members (CKLFSF1-4) are tightly linked on chromosome 16, with only 325 bp separating CKLF and CKLFSF1. We used Northern blotting and RT-PCR to show that these two genes are expressed independently of one another. We then used a novel computational promoter prediction method based on the interaction among transcription factor binding sites (TFBSs) to identify a putative promoter region for the CKLFSF1 gene.

Molecular cloning and characterization of four isoforms of mCKLF, mouse homologues of human chemokine-like factor.

Chemokine-like factor1 (CKLF1), and its three isoforms (CKLF2, 3 and 4), are recently identified human cytokines. CKLF1 is a potent chemoattractant for human leukocytes and can stimulate inflammation and the regeneration of murine skeletal muscle. CKLF2 can promote proliferation and differentiation of C2C12 muscle cells directly by inducing expression of myogenin and activating transcription factors.

Identification of eight genes encoding chemokine-like factor superfamily members 1-8 (CKLFSF1-8) by in silico cloning and experimental validation.

TM4SF11 is only 102 kb from the chemokine gene cluster composed of SCYA22, SCYD1, and SCYA17 on chromosome 16q13. CKLF maps on chromosome 16q22. CKLFs have some characteristics associated with the CCL22/MDC, CX3CL1/fractalkine, CCL17/TARC, and TM4SF proteins.

Molecular cloning and characterization of rat chemokine-like factor 1 and 2.

Chemokine-like factor 1(CKLF1) is a newly cloned cytokine with three RNA splicing isoforms. It has chemotactic activities on leukocytes and plays an important role in skeletal muscle regeneration. Here we have isolated two rat homologues of human chemokine-like factors by expressed sequence tag assembly, which are designated as rat chemokine-like factor 1 and 2 (rat CKLF1, CKLF2).

Overexpression of chemokine-like factor 2 promotes the proliferation and survival of C2C12 skeletal muscle cells.

Chemokine-like factor 1 (CKLF1) is a novel cytokine first cloned from U937 cells. It contains different splicing forms and has chemotactic effects on a wide spectrum of cells both in vitro and in vivo; it can also stimulate the regeneration of skeletal muscle cells in vivo, but the mechanism remains unclear. To probe the myogenesis function of CKLF2, which is the largest isoform of CKLFs, C2C12 murine myoblasts were stably transfected with human CKLF2 eukaryotic expression vector.