462 research outputs found
Dbl oncogene expression in MCF-10 A epithelial cells disrupts mammary acinar architecture, induces EMT and angiogenic factor secretion.
The proteins of the Dbl family are guanine nucleotide exchange factors (GEFs) of Rho GTPases and are known to be involved in cell growth regulation. Alterations of the normal function of these proteins lead to pathological processes such as developmental disorders, neoplastic transformation, and tumor metastasis. We have previously demonstrated that expression of Dbl oncogene in lens epithelial cells modulates genes encoding proteins involved in epithelial-mesenchymal-transition (EMT) and induces angiogenesis in the lens. Our present study was undertaken to investigate the role of Dbl oncogene in epithelial cells transformation, providing new insights into carcinoma progression. To assess how Dbl oncogene can modulate EMT, cell migration, morphogenesis, and expression of pro-apoptotic and angiogenic factors we utilized bi- and three-dimensional cultures of MCF-10â–‘A cells. We show that upon Dbl expression MCF-10â–‘A cells undergo EMT. In addition, we found that Dbl overexpression sustain
Prefazione dei curatori
none3prefazione al volumenoneBasello G.P.; Ognibene P.; Panaino A.Basello G.P.; Ognibene P.; Panaino A
Age-associated alterations in cholesterol homeostasis: evidence from a cross-sectional study in a Northern Italy population.
BACKGROUND:
The modifications of cholesterol metabolism associated with aging are ill-defined. The objective of this study was to define age-associated alterations of the different metabolic pathways controlling cholesterol homeostasis by analyzing circulating sterols.
METHODS:
We analyzed serum samples collected from 201 adult (75 male, 126 female) subjects within the epidemiological MICOL study (Multicentrica Italiana Colelitiasi). The age range was 38-79 years; 103 had evidence of gallstones. The concentrations of the different sterols, recognized as markers of the main pathways of cholesterol homeostasis, were analyzed by gas chromatography-mass spectrometry, including lathosterol (synthesis), campesterol and sitosterol (absorption), and 7α-hydroxy-4-cholesten-3-one (degradation to bile acids).
RESULTS:
A significant direct correlation was detected between age and cholesterol levels (r =0.34, P<0.01). The lathosterol/cholesterol ratio was lower in older age quartiles (P<0.05 by analysis of variance), with an inverse correlation between the lathosterol/cholesterol ratio and age (r=-0.32, P<0.01). Such correlation was particularly evident in females. The campesterol/cholesterol and sitosterol/cholesterol ratios were inversely correlated with aging in control, but not in gallstone patients. The levels of 7α-hydroxy-4-cholesten-3-one were not correlated with age.
CONCLUSION:
These data show a reduction of cholesterol synthesis with aging which is associated with increased circulating cholesterol levels. The finding might be related to a reduced metabolic need for cholesterol in advancing age, leading to a downregulation of the main mechanisms of cholesterol intake in the liver. A different age-related behavior was observed in gallstone-free versus gallstone patients regarding cholesterol absorption. The possible implications in terms of the pharmacological management of hypercholesterolemia in the elderly remain to be defined
Recommended from our members
Ion-Optics Calculations and Preliminary Precision Estimates of the Gas-Capable Ion Source for the 1-MV LLNL BioAMS Spectrometer
Ion-optics calculations were performed for a new ion source and injection beam line. This source, which can accept both solid and gaseous targets, will be installed onto the 1-MV BioAMS spectrometer at the Center for Accelerator Mass Spectrometry, located at Lawrence Livermore National Laboratory and will augment the current LLNL cesium-sputter solid sample ion source. The ion source and its associated injection beam line were designed to allow direct quantification of {sup 14}C/{sup 12}C and {sup 3}H/{sup 1}H isotope ratios from both solid and gaseous targets without the need for isotope switching. Once installed, this source will enable the direct linking of a nanoflow LC system to the spectrometer to provide for high-throughput LC-AMS quantitation from a continuous flow. Calculations show that, for small samples, the sensitivity of the gas-accepting ion source could be precision limited but zeptomole quantitation should be feasible
- …