Histone deacetylases (HDACs) are a diverse family of essential transcriptional regulatory enzymes, that function through the spatial and temporal recruitment of protein complexes. As the composition and regulation of HDAC complexes are only partially characterized, we built the first global protein interaction network for all 11 human HDACs in T ...

Several vectors for gene expression are available in Drosophila, a hub for genetics and genomics innovation. However, the vectors for ubiquitous expression have a complex structure, including coding exons, that makes in-frame cloning of cDNAs very complicated. In this report we describe a new Drosophila expression vector (p∆TubHA4C) for ubiquitous ...

Maternal thyroid hormones (THs) are essential for normal offspring's neurodevelopment even after onset of fetal thyroid function. This is particularly relevant for preterm children who are deprived of maternal THs following birth, are at risk of suffering hypothyroxinemia, and develop attention-deficit/hyperactivity disorder. Expression of neocortical Ca(2+)/calmodulin kinase IV (Camk4), a ...

RING finger protein 11 (RNF11), a negative regulator of NF-κB signaling pathway, colocalizes with α-synuclein and is sequestered in Lewy bodies in Parkinson's disease (PD). Since persistent NF-κB activation is reported in PD, in this report we investigated if RNF11 expression level is correlated to activated NF-κB in PD. We ...

Tetralogy of Fallot (TOF) results in chronic progressive right ventricular (RV) pressure overload and shunt hypoxemia. We investigated the global changes in the proteome of RV among infant patients with and without TOF to gain an insight into early RV remodeling. One hundred and thirty-six differentially expressed proteins were identified ...

We have demonstrated a detection method for the ultra-sensitive detection of an mRNA biomarker. The method utilizes functionalized magnetic nanoparticles (MNPs) for signal enhancement in conjunction with surface plasmon resonance (SPR) on gold nanoslits. The approach for detection includes double hybridization at two different specific locations in two steps. First, ...

Myosin IC is a single headed member of the myosin superfamily that localizes to the cytoplasm and the nucleus, where it is involved in transcription by RNA polymerases I and II, intranuclear transport, and nuclear export. Three isoforms of myosin IC are expressed in mammalian cells that differ only in ...

In the primer extension assay, the transcription start site for a gene is determined experimentally by identifying the 5' end of the encoded messenger RNA (mRNA). The protocol begins with a primer, usually a synthetic oligonucleotide of about 20 residues, that is complementary to an mRNA sequence ∼50-150 nucleotides downstream ...

Live-cell imaging of mRNA yields important insights into gene expression, but it has generally been limited to the labeling of one RNA species and has never been used to count single mRNAs over time in yeast. We demonstrate a two-color imaging system with single-molecule resolution using MS2 and PP7 RNA ...

Germ cells differentiate into oocytes in females and are arrested at the first meiotic prophase. However, during arrest, oocytes undergo a growth phase leading to a dramatic increase in size, which is under control of transcription events. In the current study, we examined the transcriptional activity of growing pig oocytes ...

MicroRNAs (miRNAs) are small non-coding RNAs that play important roles in post-transcriptional regulation of gene expression. Mature miRNAs associate with the RNA interference silencing complex (RISC) to repress mRNA translation and/or degrade mRNA transcripts. Mass spectrometry-based proteomics has enabled identification of several core components of the canonical miRNA processing pathway ...

Drosophila mutants black (b) and ebony (e) show pigmentation defects in the adult cuticle, which disclose their co-operative activity in β-alanyl-dopamine formation. In visual signal transduction Ebony conjugates β-alanine to histamine forming β-alanyl-histamine, or carcinine. Mutation of ebony disrupts signal transduction and reveals an electroretinogram (ERG) phenotype. In contrast to ...

Alcohol abuse is one of the most common factors associated with acute and chronic pancreatitis. Although it is evident that alcohol abuse can have an important role in the development of pancreatitis, it does not seem that alcohol abuse alone is responsible for this disease. We investigated the involvement of ...

Interferon-beta (IFN-β) is a critical antiviral cytokine and is essential for innate and acquired immune responses to pathogens. Treatment with polyinosinic:polycytidylic acid (poly(I:C)) induces transient accumulation of IFN-β mRNA, which involves an increase and a decrease of IFN-β mRNA. This phenomenon has been extensively analyzed as a model for understanding ...

Matrix metalloproteinase (MMP) is involved in the upper airway remodeling process. We hypothesized that MMP had an additive effect on the formation of recurrent nasal polyp. We also investigated the association between the functional promoter polymorphism of MMPs and the intensity of labeling index. Expressions of MMP-2 and MMP-9 were ...

Transcription in higher organisms requires spatiotemporal coordination of transcription machinery and the transcription factors at promoter sites. Toward this, recent evidence suggests that both static compartmentalization and dynamic self-organization of transcriptional apparatus are in effect at sites of transcription. Although the dynamics of transcription machinery is essential to genome regulation, ...

As an underlying mechanism of antenatal maternal malnutrition-induced type 2 diabetes mellitus (T2DM), alterations in the local pancreatic renin-angiotensin system (RAS) may play a significant role. We tested the hypothesis that antenatal maternal protein deprivation (AMPD) leads to increased activity of the local pancreatic RAS, with associated hyperglycemia in the ...

OBJECTIVES: Pancreatic stellate cells (PSCs) play a pivotal role in pancreatic fibrosis associated with chronic pancreatitis and pancreatic cancer. Connexins (Cxs) allow direct intercellular communications as components of gap junction but also play important roles in the regulation of cell proliferation, cell differentiation, and tissue development. We here examined the ...

OBJECTIVE: GPR119 is reportedly involved in regulating glucose metabolism and food intake in rodents, but little is known about its expression and functional significance in humans. To begin to assess the potential clinical importance of GPR119, the distribution of GPR119 gene expression in humans was examined. MATERIALS/METHODS: Expression of GPR119 ...

Apoptosis is one of the core signaling pathways disrupted in pancreatic ductal adenocarcinoma (PDA). Death receptor 5 (DR5) is a member of the tumor necrosis factor (TNF)-receptor superfamily that is expressed in cancer cells. Binding of TNF-related apoptosis-inducing ligand (TRAIL) to DR5 is a potent trigger of the extrinsic apoptotic ...

OBJECTIVES: Investigation of expression profile of well-established microRNAs in pancreatic adenocarcinoma, and its correlation with clinicopathological factors. METHODS: Eighty-eight samples of ductal pancreatic adenocarcinoma and 98 control samples were analyzed by real-time polymerase chain reaction for miR-21, miR-31, miR-122, miR-145, miR-146a, miR-155, miR-210, and miR-222 expressions. The results were normalized ...

ABSTRACT: BACKGROUND: It has been reported that the histone deacetylase inhibitor (iHDAc) trichostatin A (TSA) induces an increase in MDR1 gene transcription (ABCB1). This result would compromise the use of iHDACs in combination with other cytotoxic agents that are substrates of P-glycoprotein (Pgp). It has also been reported the use ...

Mutationally activated KRAS, detected in ~90% of pancreatic ductal adenocarcinomas (PDAs), has proven an intractable pharmacologic target to date. Consequently, efforts to treat KRAS mutated cancers are focused on targeting RAS-regulated signaling pathways. In mouse models, expression of BRAFV600E combined with dominant-negative TP53 elicits PDA, and pharmacologic blockade of MEK ...

Arachidonic acid is converted to prostaglandin E(2) (PGE(2)) by a sequential enzymatic reaction performed by two isoenzyme groups, cyclooxygenases (COX-1 and COX-2) and terminal prostaglandin E synthases (cPGES, mPGES-1, and mPGES-2). mPGES-1 is widely considered to be the final enzyme regulating COX-2-dependent PGE(2) synthesis. These generalizations have been based in ...

MUC4 is a type-1 transmembrane mucin differentially expressed in multiple cancers and has previously been shown to potentiate progression and metastasis of pancreatic cancer. In this study, we investigated the molecular mechanisms associated with the MUC4-induced invasion and metastasis in pancreatic cancer. Stable silencing of MUC4 in multiple pancreatic cancer ...

Cyclooxygenase-2 (COX-2) is upregulated in pancreatic ductal adenocarcinomas (PDAC). However, how COX-2 promotes PDAC development is unclear. While previous studies have evaluated the efficacy of COX-2 inhibition via the use of non steroidal anti-inflammatory drugs (NSAIDs) or the COX-2 inhibitor celecoxib in PDAC models, none have addressed the cell intrinsic ...

There are seven distinct β-tubulin isotypes and eight α-tubulin isotypes in mammals that are hypothesized to have tissue- and cell-specific functions. There is an interest in the use of tubulin isotypes as prognostic markers of malignancy. βV-tubulin, like βIII-tubulin, has been implicated in malignant transformation and drug resistance, however little ...

A lack of expression of miR-143 and miR-145 has been demonstrated to be a frequent feature of colorectal tumors. Activating KRAS mutations have been reported in 30-60% of colorectal cancers and an inverse correlation between Kras and miR-143/145 expression has been observed. Previously, we have demonstrated that oncogenic Kras leads ...

Pancreatic carcinoma, a leading cause of cancer death, is thought to develop out of pancreatic intraepithelial neoplasia (PanIN). PanIN lesions have not yet attained the fully malignant phenotype, but show increased proliferation and dysplasia, and frequently bear an oncogenic KRAS mutation. Pancreatic cancer development is associated with increased activity of ...

The present study evaluated the potential role of lysophosphatidic acid receptors (lpars) in processes leading to local invasiveness and metastasis in Chinese pancreatic carcinoma. Real-time reverse-transcriptase polymerase chain reaction and Western blot analysis were used to detect expression of lpars in tumour and adjacent non-tumour tissues from patients with surgically ...

MCC-555 is a novel PPARα/γ dual ligand of the thiazolidinedione class and was recently developed as an anti-diabetic drug with unique properties. MCC-555 also has anti-proliferative activity through growth inhibition and apoptosis induction in several cancer cell types. Our group has shown that MCC-555 targets several proteins in colorectal tumorigenesis ...

FSH receptor (FSHR) expression is restricted to gonads, where it drives FSH-dependent cell differentiation; in addition, FSHR plays an important role in the regulation of ovarian angiogenesis. Recently, FHSR expression has been shown in blood vessels of various tumours. However, pancreatic neuroendocrine tumours (p-NET), which have high degree blood supply, ...

The recent decades have seen a huge expansion in our knowledge about pancreatic development. Numerous lineage-restricted transcription factor genes have been identified and much has been learned about their function. Similarly, numerous signaling pathways important for pancreas development have been identified and the specific roles have been investigated by genetic ...

OBJECTIVES: The peroxisome proliferator-activated receptor-α (PPAR-α) has attracted considerable attention for its anti-inflammatory properties; however, Toll-like receptor (TLR) pathways have an essential proinflammatory role in acute pancreatitis (AP). This study aimed to evaluate the attenuation of inflammation by PPAR-α and to investigate the interaction between PPAR-α and TLR pathways in ...

The transition from gestation to lactation is characterized by a robust adaptation of maternal pancreatic β-cells. Consistent with the loss of β-cell mass, glucose-induced insulin secretion is down-regulated in the islets of early lactating dams. Extensive experimental evidence has demonstrated that the surge of prolactin is responsible for the morphofunctional ...

Somatostatin receptor subtype 5 (SSTR5) mediates the inhibitory effect of somatostatin and its analogs on insulin expression/secretion and islet cell proliferation. We provide biochemical and genetic evidence that SSTR5 exerted its physiological actions via down-regulating pancreatic and duodenal homeobox-1 (PDX-1), a β-cell-specific homeodomain-containing transcription factor. Cotransfection of SSTR5 with PDX-1 ...

Gap junctions and gap junction communication have long been recognized to play roles in tissue organization and remodeling through both cell autonomous and intercellular means. We hypothesized that these processes become dysregulated during pancreas cancer progression. Molecular and histological characterization of the gap junction protein, connexin43, during progression of pancreatic ...

Pancreatic cancer is a devastating disease with the worst mortality rate. Therefore, a rational strategy for future drug development is critical. Genistein is a small, biologically active flavonoid that is found in high amounts in soy. This important compound supports a wide variety of biological activities, but is best known ...

Membrane type-1 matrix metalloproteinase (MT1-MMP) is often activated and expressed in tumor cells with significant invasive properties, and is associated with poor prognosis of patients. This could partly be due to deregulated expression of microRNAs (miRNAs) which regulates the expression of MT1-MMP and PTEN (phosphatase and tensin homolog) contributing to ...

CX3CL1 is a member of the chemokine family, and its receptor, CX3CR1, is expressed in pancreatic ductal adenocarcinoma. However, it is unclear whether there is a correlation between the expression of CX3CL1/CX3CR1 axis and the prognosis of patients with pancreatic ductal adenocarcinoma. Tissue microarray and immunohistochemistry were used to study ...

Because we found in a recent study that pancreatic adenocarcinoma up-regulated factor (PAUF), a novel oncogene, induces a rapid proliferation of pancreatic cells by up-regulation of β-catenin, we postulated that β-catenin might be a target molecule for pancreatic cancer treatment. We thus speculated whether SIRT1, known to target β-catenin in ...

Molecule targeting therapy using somatostatin (SS) analogues has become a widely accepted modality to treat neuroendocrine tumors (NETs), particularly gastrointestinal (GI) and pancreatic endocrine tumors. On the other hand, little is known about the expression of somatostatin receptor (SSTR) subtypes in neuroendocrine carcinomas (NECs). We investigated the expression of SSTR ...

Ezrin-radixin-moesin-binding phosphoprotein 50 (EBP50) is a putative tumor suppressor that is correlated with many human cancers. However, the function of EBP50 in pancreatic cancer (PC) has not been described. In this paper, the EBP50 expression level in PC tissues was characterized. In vitro, the effects of EBP50 down-regulation by siRNA ...

Pancreatic ductal adenocarcinoma (PDAC) is characterized by overexpression of enhancer of Zeste homolog-2 (EZH2), which plays a pivotal role in cancer stem cell (CSC) self-renewal through methylation of histone H3 lysine-27 (H3K27me3). Against this background, EZH2 was identified as an attractive target, and we investigated the interaction of the EZH2 ...

Nkx2.2 encodes a homeodomain transcription factor required for the correct specification and/or differentiation of cells in the pancreas, intestine, and central nervous system (CNS). To follow the fate of cells deleted for Nkx2.2 within these tissues, we generated Nkx2.2:lacZ knockin mice using a recombination-mediated cassette exchange (RMCE) approach. Expression analysis ...

Expression of early growth response protein (Egr)-1, a protein of the Egr family of zinc finger transcription factors, is stimulated in glucose-treated pancreatic β-cells and insulinoma cells. The purpose of this study was to elucidate the role of Egr transcription factors in pancreatic β-cells in vivo. To overcome the problem ...

Igarashi S, Matsubara T, Harada K, Ikeda H, Sato Y, Sasaki M, Matsui O & Nakanuma Y (2012) Histopathology Bile duct expression of pancreatic and duodenal homeobox 1 in perihilar cholangiocarcinogenesis Aims:  Pancreatic and duodenal homeobox 1 (Pdx1) is a transcription factor that is crucial in embryogenic development and differentiation ...

Liver and ventral pancreas develop from neighboring territories within the endoderm of gastrulae. ventral pancreatic precursor 1 (vpp1) is a marker gene that is differentially expressed in a cell population within the dorsal endoderm in a pattern partially overlapping with that of hematopoietically expressed homeobox (hhex) during gastrulation. In tail ...

The fluorinated analog of deoxycytidine, Gemcitabine (Gemzar), is the main chemotherapeutic drug in pancreatic cancer, but survival remains weak mainly because of the high resistance of tumors to the drug. Recent works have shown that the mucin MUC4 may confer an advantage to pancreatic tumor cells by modifying their susceptibility ...

Receptor-associated protein 80 (RAP80) increases substantially in pancreatic cancer. The involvement of RAP80 in the chemoresistance of pancreatic cancer should be elucidated. We investigated the effects of inhibiting RAP80 expression on the sensitivity of pancreatic cancer cells to gemcitabine chemotherapy by using small interfering RNA (siRNA). Chemically synthesized siRNA RAP80 ...