SOX2 Is an Oncogene Activated by Recurrent 3q26.3 Amplifications in Human Lung Squamous Cell Carcinomas

Squamous cell carcinoma (SCC) of the lung is a frequent and aggressive cancer type. Gene amplifications, a known activating mechanism of oncogenes, target the 3q26-qter region as one of the most frequently gained/amplified genomic sites in SCC of various types. Here, we used array comparative genomic hybridization to delineate the consensus region of 3q26.3 amplifications in lung SCC. Recurrent amplifications occur in 20% of lung SCC (136 tumors in total) and map to a core region of 2 Mb (Megabases) that encompasses SOX2, a transcription factor gene. Intense SOX2 immunostaining is frequent in nuclei of lung SCC, indicating potential active transcriptional regulation by SOX2. Analyses of the transcriptome of lung SCC, SOX2-overexpressing lung epithelial cells and embryonic stem cells (ESCs) reveal that SOX2 contributes to activate ESC-like phenotypes and provide clues pertaining to the deregulated genes involved in the malignant phenotype. In cell culture experiments, overexpression of SOX2 stimulates cellular migration and anchorage-independent growth while SOX2 knockdown impairs cell growth. Finally, SOX2 over-expression in non-tumorigenic human lung bronchial epithelial cells is tumorigenic in immunocompromised mice. These results indicate that the SOX2 transcription factor, a major regulator of stem cell function, is also an oncogene and a driver gene for the recurrent 3q26.33 amplifications in lung SCC

Specific electrochemical sensor for cadmium detection: Comparison between monolayer and multilayer functionalization

Selective and sensitive cadmium sensors were prepared by functionalizing glassy carbon electrodes (GCE) using the electrochemical reduction of p-benzoic acid diazonium salts according to either a multilayer or a monolayer coating process. Such modified electrodes were then post-functionalized with 1,2-bis-[o-aminophenylthio]ethane (APTE) or its monoprotected derivative leading to specific Cd2+ electrochemical sensors. The step by step preparation of the electrodes as well as the ability of the immobilized receptor to complex Cd2+ was investigated by XPS and Raman spectroscopy. The detection and quantification of cadmium was performed in two steps: the preconcentration of Cd2+ ions by complexation with immobilized APTE and the analysis by Linear Sweep Stripping Voltammetry (LSSV). More importantly, multilayer versus monolayer grafting has a strong influence on the sensor performances. Whereas calibration curves typical of an equilibrium process were obtained for sensors realized with multilayer organic films, sensors with a monolayer organic film led to linear calibration curves, in the same concentration range. Finally, the monolayer sensor gave a lower limit of detection (LOD) and highlighted better selectivity than unmodified electrode