BackgroundWe have previously reported significant downregulation of ubiquitin carboxyl-terminal hydrolase 1 (UCHL1) in prostate cancer (PCa) compared to the surrounding benign tissue. UCHL1 plays an important role in ubiquitin system and different cellular processes such as cell proliferation and differentiation. We now show that the underlying mechanism of UCHL1 downregulation in PCa is linked to its promoter hypermethylation. Furthermore, we present evidences that UCHL1 expression can affect the behavior of prostate cancer cells in different ways.ResultsMethylation specific PCR analysis results showed a highly methylated promoter region for UCHL1 in 90% (18/20) of tumor tissue compared to 15% (3/20) of normal tissues from PCa patients. Pyrosequencing results confirmed a mean methylation of 41.4% in PCa whereas only 8.6% in normal tissues. To conduct functional analysis of UCHL1 in PCa, UCHL1 is overexpressed in LNCaP cells whose UCHL1 expression is normally suppressed by promoter methylation and found that UCHL1 has the ability to decrease the rate of cell proliferation and suppresses anchorage-independent growth of these cells. In further analysis, we found evidence that exogenous expression of UCHL1 suppress LNCaP cells growth probably via p53-mediated inhibition of Akt/PKB phosphorylation and also via accumulation of p27kip1 a cyclin dependant kinase inhibitor of cell cycle regulating proteins. Notably, we also observed that exogenous expression of UCHL1 induced a senescent phenotype that was detected by using the SA-ß-gal assay and might be due to increased p14ARF, p53, p27kip1 and decreased MDM2.ConclusionFrom these results, we propose that UCHL1 downregulation via promoter hypermethylation plays an important role in various molecular aspects of PCa biology, such as morphological diversification and regulation of proliferation.

Prostate cancer (PCa) is the most common type of cancer found in men and among the leading causes of cancer death in the western world. In the present study, we compared the individual protein expression patterns from histologically characterized PCa and the surrounding benign tissue obtained by manual micro dissection using highly sensitive two-dimensional differential gel electrophoresis (2D-DIGE) coupled with mass spectrometry. Proteomic data revealed 118 protein spots to be differentially expressed in cancer (n = 24) compared to benign (n = 21) prostate tissue. These spots were analysed by MALDI-TOF-MS/MS and 79 different proteins were identified. Using principal component analysis we could clearly separate tumor and normal tissue and two distinct tumor groups based on the protein expression pattern. By using a systems biology approach, we could map many of these proteins both into major pathways involved in PCa progression as well as into a group of potential diagnostic and/or prognostic markers. Due to complexity of the highly interconnected shortest pathway network, the functional sub networks revealed some of the potential candidate biomarker proteins for further validation. By using a systems biology approach, our study revealed novel proteins and molecular networks with altered expression in PCa. Further functional validation of individual proteins is ongoing and might provide new insights in PCa progression potentially leading to the design of novel diagnostic and therapeutic strategies.

Triphenyltin(IV) halides, Ph3SnHal with Hal = Cl, Br, and I, are white, low melting solids soluble in many indifferent organic solvents like chloroform or toluene. In these solutions as well as in solid they consist of isolated, tetrahedral molecules which intermolecular interactions restricted to van-der Waals ones. These molecules are characterized through the three aromatic phenyl rings attached at a certain pitch angle around the shaft of the tin-halide bond giving them a propeller-like shape accompanied by molecular chirality as the normal vectors of the blades can be oriented clock-wise or anti-clock-wise with respect to the tin-halide bond. In the past, a lot of different polymorphs of triphenyltin(IV) halides with up to 24 molecules in the unit cell have been described, all crystallizing in centrosymmetric space groups, implying that both chiral molecules are present. From a structural point of view there are still several questions of general interest: (i) how are both enantiomers distributed in these polymorphs, (ii) how are the molecular dipole moments arranged, and (iii) how are the different polymorphs related to each other. During various studies on the syntheses and reactivity of triphenyltin(IV) halides we found four additional polymorphs, which constitute new structure types in case of δ-Ph3SnI (Z = 8, monoclinic, P21/c), and ε-Ph3SnI (Z = 12, monoclinic, P21/c) or complete the already existing α-Ph3SnCl structure type (Z = 24, rhomboedric, R-3) in case of β-Ph3SnBr and ζ-Ph3SnI. Analysing the new and already known polymorphs with respect to the three questions mentioned above points out (i) the influence of crystal symmetry elements (screw axes and glide planes) as well as (ii) the importance of the formation of supramolecular dimers composed of both enantiomers with an antiparallel orientation of the two molecular dipole moments, on the different structure types formed and their relation among each other.https://www.eiseverywhere.com/retrieveupload.php?c3VibWlzc2lvbl81OTI4NF8zNTQ2MDMuanBnKmVzZWxlY3Q=