Activation of the pro-migratory bone morphogenetic protein receptor 1B gene in human MDA-MB-468 triple-negative breast cancer cells that over-express CYP2J2

Secondary metastases are the leading cause of mortality in patients with breast cancer. Cytochrome P450 (CYP) 2J2 (CYP2J2) is upregulated in many human tumors and generates epoxyeicosanoids from arachidonic acid that promote tumorigenesis and metastasis, but at present there is little information on the genes that mediate these actions. In this study MDA-MB-468 breast cancer cells were stably transfected with CYP2J2 (MDA-2J2 cells) and Affymetrix microarray profiling was undertaken. We identified 182 genes that were differentially expressed in MDA-2J2 cells relative to control (MDA-CTL) cells (log[fold of control] ≥2). From gene ontology pathway analysis bone morphogenetic protein (BMP) receptor 1B (BMPR1B) emerged as an important upregulated gene in MDA-2J2 cells. Addition of the BMPR1B ligand BMP2 stimulated the migration of MDA-2J2 cells, but not MDA-CTL cells, from 3D-matrigel droplets. Migration of MDA-2J2 cells was prevented by the BMPR antagonist dorsomorphin. These findings indicate that over-expression of CYP2J2 in MDA-MB-468-derived breast cancer cells activates BMPR1B expression that may contribute to increased migration. Targeting BMPR1B may be a novel approach to inhibit the metastatic activity of breast cancers that contain high levels of CYP2J2.     

Alternative rib bone biopsy measurements to estimate changes in skeletal mineral reserves in cattle

Rib bone biopsy samples are often used to estimate changes in skeletal mineral reserves in cattle but differences in sampling procedures and the bone measurements reported often make interpretation and comparisons among experiments difficult. ‘Full-core’ rib bone biopsy samples, which included the external cortical bone, internal cortical bone and trabecular bone (CB_ext, CB_int and Trab, respectively), were obtained from cattle known to be in phosphorus (P) adequate (P_adeq) or severely P-deficient (P_defic) status. Experiments 1 and 2 examined growing steers and Experiment 3 mature breeder cows. The thickness of cortical bone, specific gravity (SG), and the amount and concentration of ash and P per unit fresh bone volume, differed among CB_ext, CB_int and Trab bone. P concentration (mg/cc) was closely correlated with both SG and ash concentrations (pooled data, r=0.99). Thickness of external cortical bone (CBT_ext) was correlated with full-core P concentration (FC-P_conc) (pooled data, r=0.87). However, an index, the amount of P in CB_ext per unit surface area of CB_ext (PSACB; mg P/mm²), was more closely correlated with the FC-P_conc (pooled data, FC-P_conc=37.0+146×PSACB; n=42, r=0.94, RSD=7.7). Results for measured or estimated FC-P_conc in 10 published studies with cattle in various physiological states and expected to be P_adeq or in various degrees of P_defic status were collated and the ranges of FC-P_conc indicative of P adequacy and P deficiency for various classes of cattle were evaluated. FC-P_conc was generally in the range 130 to 170 and 100 to 120 mg/cc fresh bone in P_adeq mature cows and young growing cattle, respectively. In conclusion, the FC-P_conc could be estimated accurately from biopsy samples of CB_ext. This allows comparisons between studies where full-core or only CB_ext biopsy samples of rib bone have been obtained to estimate changes in the skeletal P status of cattle and facilitates evaluation of the P status of cattle.     

The role of lipid second messengers in aldosterone synthesis and secretion

Second messengers are small rapidly diffusing molecules or ions that relay signals between receptors and effector proteins to produce a physiological effect. Lipid messengers constitute one of the four major classes of second messengers. The hydrolysis of two main classes of lipids, glycerophospholipids and sphingolipids, generate parallel profiles of lipid second messengers: phosphatidic acid (PA), diacylglycerol (DAG), and lysophosphatidic acid versus ceramide, ceramide-1-phosphate, sphingosine, and sphingosine-1-phosphate, respectively. In this review, we examine the mechanisms by which these lipid second messengers modulate aldosterone production at multiple levels. Aldosterone is a mineralocorticoid hormone responsible for maintaining fluid volume, electrolyte balance, and blood pressure homeostasis. Primary aldosteronism is a frequent endocrine cause of secondary hypertension. A thorough understanding of the signaling events regulating aldosterone biosynthesis may lead to the identification of novel therapeutic targets. The cumulative evidence in this literature emphasizes the critical roles of PA, DAG, and sphingolipid metabolites in aldosterone synthesis and secretion. However, it also highlights the gaps in our knowledge, such as the preference for phospholipase D-generated PA or DAG, as well as the need for further investigation to elucidate the precise mechanisms by which these lipid second messengers regulate optimal aldosterone production.     

Isolation and characterization of a human hepatic epithelial-like cell line (AKN-1) from a normal liver

Summary The isolation and characterization of human liver cell lines are rather difficult due to limited material and poor growth in cell culture. In this report, we present the isolation, culture and characterization of a new epithelial-like liver cell line (AKN-1) with a heterogeneous cell population and many characteristics of the biliary epithelium. The AKN-1 cell line stained positively with antibodies to epithelial cytokeratin polypetides CK 8, 18, and 19. In addition, the cell line expressed the anti-human epithelial-related antigen (MOC-31), the human epithelial antigen (HEA), and the gamma-glutamyl transpeptidase, the hematopoietic growth factor, stem cell factor, and also its receptor, c-kit. The cell line failed to express albumin and factor 8 by immunohistochemistry. It did show, however, a twofold increase in 7-ethoxyresorufin-O-deethylase activity. Cytogenetic characterization revealed rare breakpoints in chromosome 2, which to our knowledge, have not yet been reported in liver cells.     

Reducing acetylated tau is neuroprotective in brain injury

1. Download : Download high-res image (138KB)
2. Download : Download full-size image

     

Fruit thinning plums and apricots

The need for crop load reduction to improve fruit size andconsistency of cropping on plum and apricot trees is discussed. Threealternative strategies of achieving this objective are described: byinhibition of flowering, prevention of fruit set or stimulation ofincreased fruitlet abscission. Methods of achieving each of thesestrategies, by manual, mechanical or chemical means are discussed andevaluated.