Galectin-3 (GAL3), a ␤-galactoside-binding lectin, confers chemoresistance to a wide variety of cancer cell types. It may exhibit anti-or pro-apoptotic activity depending on the nature of the stimulus. We report here that introducing phosphorylated galectin-3 (P-GAL3) into GAL3-null, tumor necrosis factorrelated apoptosis-inducing ligand (TRAIL)-resistant human breast carcinoma cells promotes TRAIL-induced apoptotic cell death by stimulating the phosphorylation/inactivation of the pro-apoptotic molecule Bad resulting in the inhibition of mitochondrial depolarization and the release of cytochrome c. Exposure of the transfectant cells to TRAIL leads to the recruitment of the initiator capase-8 followed by activation of the effector caspase-9, independent of cytochrome c, and subsequently the processing of the executioner caspase-3. P-GAL3 and phosphatase and tensin homologue deleted on chromosome 10 (PTEN) were coordinately expressed, with concomitant dephosphorylation of Akt in TRAIL-sensitive cells. In contrast, overexpression of phospho-mutant GAL3 (incapable of phosphorylation) failed to elicit similar responses. Depletion of PTEN using small interference RNAs reinstated Akt phosphorylation and conferred TRAIL resistance. In addition phosphatidylinositol 3-kinase inhibitors rendered the phospho-mutant GAL3-resistant cells sensitive to TRAIL. These findings suggest a pivotal role for P-GAL3 in promoting TRAIL sensitivity through activation of a nonclassic apoptotic pathway and identify P-GAL3 as a novel regulator of PTEN.

Background Bile reflux contributes to the development of esophageal injury and neoplasia. MUC5AC mucin is absent in the normal squamous epithelium of the esophagus but strongly expressed in Barrett’s esophagus (BE). The aim of this study was to determine whether and how bile acids influence the expression of MUC5AC in the esophagus. Methods MUC5AC expression was studied by immunohistochemistry and immunoblotting in human tissues, tissues from a rat model of BE, and in SKGT-4 cultured esophageal epithelial cells. MUC5AC transcription was studied by real-time PCR and transient transfection assays. Results MUC5AC was absent from normal squamous epithelium but present in 100% of Barrett’s specimens and in 61.5% of human esophageal adenocarcinoma tissues examined. MUC5AC protein expression was induced to a greater degree by conjugated bile acids than by unconjugated bile acids, and this occurred at the transcriptional level. In the rat reflux model, MUC5AC mucin was abundantly expressed in tissues of BE stimulatesd by duodenoesophageal reflux. Conjugated bile acids induced AKT phosphorylation in SKGT-4 cells, but had no effects on ERK1/2, JNK, and P-38 kinase phosphorylation. The PI3K inhibitor LY294002 and a dominant-negative AKT construct prevented the induction of MUC5AC by conjugated bile acids. Transactivation of AP-1 by conjugated bile acids coincided with MUC5AC induction, and co-transfection with a dominant-negative AP-1 vector decreased MUC5AC transcription and its induction. Conclusions Conjugated bile acids in the bile refluxate contribute to MUC5AC induction in the esophagus. This occurs at the level of transcription, and involves activation of the PI3K/AKT/AP-1 pathway.

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Wind erosion may appear because of the construction of embankment in a non-wind-eroded area. It can cause the destruction of the embankment and bring about flying dust, to which little attention has been paid. Based on analysis of the embankment-caused acceleration of wind, a design method under consideration of wind erosion is put forward for embankment in the non-wind-eroded area. Then protection range for the embankment is suggested and countermeasures against wind erosion are given. The results of this paper help render the design of embankment more reasonable and environmentally friendly.