The adenomatous polyposis coli (APC) gene product is mutated in the vast majority of human colorectal cancers. APC negatively regulates the WNT pathway by aiding in the degradation of beta-catenin, which is the transcription factor activated downstream of WNT signaling. APC mutations result in beta-catenin stabilization and constitutive WNT pathway activation, leading to aberrant cellular proliferation. APC mutations associated with colorectal cancer commonly fall in a region of the gene termed the mutation cluster region and result in expression of an N-terminal fragment of the APC protein. Biochemical and molecular studies have revealed localization of APC/Apc to different sub-cellular compartments and various proteins outside of the WNT pathway that associate with truncated APC/Apc. These observations and genotype-phenotype correlations have led to the suggestion that truncated APC bears neomorphic and/or dominant-negative function that support tumor development. To analyze this possibility, we have generated a novel allele of Apc in the mouse that yields complete loss of Apc protein. Our studies reveal that whole-gene deletion of Apc results in more rapid tumor development than the APC multiple intestinal neoplasia (Apc(Min)) truncation. Furthermore, we found that adenomas bearing truncated Apc had increased beta-catenin activity when compared with tumors lacking Apc protein, which could lead to context-dependent inhibition of tumorigenesis. Oncogene (2010) 29, 1857-1864; doi:10.1038/onc.2009.457; published online 14 December 2009

Molluscan hemocyanins are very large biological macromolecules and they act as oxygen-transporting glycoproteins. Most of them are glycoproteins with molecular mass around 9000 kDa. The oligosaccharide structures of the structural subunit RvH2 of Rapana venosa hemocyanin (RvH) were studied by sequence analysis of glycans using MALD1-TOF-MS and tandem mass spectrometry on a Q-Trap mass spectrometer after enzymatical liberation of the N-glycans from the polypeptides. Our study revealed a highly heterogeneous mixture of glycans of the compositions Hex(0-9) HexNAc(2-4) Hex(0-3) Pent(0-3) Fuc(0-3). A novel type of N-glycan, with an internal fucose residue connecting one GaINAc(beta 1-2) and one hexuronic acid, was detected, as also occurs in subunit RvH1. A glycan with the same structure but with two deoxyhexose residues was observed as a doubly charged ion. Antiviral effects of the native molecules of RvH and also of Helix lucorum hemocyanin (HIH), of their structural subunits, and of the glycosylated functional unit RvH2-e and the non-glycosylated unit RvH2-c on HSV virus type 1 were investigated. Only glycosylated FU RvH2-e exhibits this antiviral activity. The carbohydrate chains of the FU are likely to interact with specific regions of glycoproteins of HSV, through van der Waals interactions in general or with certain amino acid residues in particular. Several clusters of these residues can be identified on the surface of RvH2-e. (C) 2010 Elsevier Ltd. All rights reserved.

The structure of 2-carboxyindan-1,3-dione was investigated using a combination of quantum-chemical calculations and solid-state NMR and IR spectroscopy. Due to poor solubility of the compound in different solvents, no single crystals could be obtained. Two dimeric structures formed from the tautomers of 2-carboxyindan-1,3-dione are likely to coexist in the solid state. The dimers interconvert via intramolecular proton transfer in one of the tautomeric forms constituting the dimers. The energy barrier of the intramolecular proton transfer reaction is calculated as 5.82 kcal mol(-1) at the MP2/6-31++G level of theory.

A novel N-substituted 4-methoxy-1,8-naphthalimide (NAFTA 8) especially designed for fluorescent labeling of gold nanoparticles has been synthesized. NAFTA 8 bears a long methylene chain at the imide N atom and has a terminal SH group, which enables its chemical binding to gold nanostructures. The longest wavelength absorption maximum of NAFTA 8 in chloroform is at 370 nm, the fluorescent maximum is at 430 nm and the fluorescent quantum yield is 0.95. The newly synthesized fluorophore is applied for functionalization of gold nanoparticles with diameter 1.5 +/- 0.5 nm prepared through chemical reduction. The obtained Monolayer Protected Clusters are characterized by elemental analysis, TEM. XPS, FT-IR, absorption and fluorescence spectroscopy. The performed investigations provide evidence for the formation of chemical bond between the thiol ligand and the gold surface. They also show that the obtained metal/dielectric 3D structures are highly fluorescent. (C) 2010 Elsevier B.V. All rights reserved.

A set of newly synthesized aryl-substituted amides of 16-mercaptohexadecanoic acid (R = 4-OH; 3,5-di-OH) are self-assembled on Au(111) substrate. Self assembled monolayers (SAMs) formed by these molecules are studied by ellipsometry from infrared to visible spectral range. Best fit calculations based on the three-phase optical model are employed in order to determine the average tilt angle of the hydrocarbon chains. The data revealed that the SAMs reside in a crystalline-like environment as the long methylene chains predominantly exist in all-trans conformation. The calculated tilt angle of the hydrocarbon chain is decreased by approximately 12 degrees. in comparison with the one for the correspondent long-chain n-alkyl thiols. Strong hydrogen bonded networks were detected between the amide proton and the carbonyl oxygen as well as between hydroxyl groups in the end aryl substituents. The transition dipole moments of the C=O, N-H and O-H modes are oriented almost parallel to the gold surface.

Gene expression data from an adenocarcinoma derived cell line.

Gene expression data from an adenocarcinoma derived cell line following reactivation of p53 expression by tamoxifen treatment.

Gene expression data from an adenocarcinoma derived cell line.