Aberrant Signal transducers and activators of transcription-3 (STAT3) signaling pathway is a major cause of tumor invasion and metastasis; the underlying mechanisms, however, are not well understood. Epithelial-mesenchymal transition (EMT) is an early event that occurs during invasion of cancers of an epithelial origin. It remains elusive whether STAT3signaling pathway is involved in EMT. The objective of this study was to evaluate the effect of blockage of STAT3 signaling pathway on IL-6 inducing EMT in human pancreatic cancer cells. We used SW1990 cells and induced them to undergo EMT by exposing these cells to soluble factor interleukin-6 (IL-6). The expression of Snail, E-cadherin, and Twist was detected by reverse transcription-PCR, real-time PCR, and Western blotting. Cell morphology was observed under invert phase-contrast microscope.The invasion ability was determined by cell invasion assay in vitro. Our results demonstrated that STAT3 signaling pathway was involved in pancreatic cancer cell invasion and EMT, and that EMT induced by IL-6 was associated with the activation of STAT3 signaling pathway. Inhibition of STAT3 signaling pathway by silencing of the STAT3 gene with RNAi blocked STAT3 signaling pathway activation and suppressed EMT in pancreatic cancer cells. Collectively, the STAT3 signaling pathway plays an important role in the process of EMT of pancreatic cancer by regulating Snail gene expression. Better understanding of STAT3 signaling pathways in EMT may contribute to development of novel therapeutic strategies in invasion and metastasis of pancreatic cancer.

Surfactant protein C (SP-C; mouse genomic designation, Sftpc) is a hydrophobic peptide that enhances the spreading and stability of surfactant phospholipids at the air-liquid interface during the respiratory cycle in the lung. Expression of the Sftpc gene is restricted to the distal respiratory epithelium during branching morphogenesis of the fetal lung and to alveolar type II (TII) epithelial cells in the postnatal lung. TII cell-specific regulatory elements were identified within Ϫ215 bp of the human SP-C promoter in transgenic mice (14). This region of the proximal promoter is highly homologous between humans and mice, containing conserved binding sites for nuclear factor I (NFI) (3) and thyroid transcription factor 1 (TTF-1; also termed T-EBP and Nkx2.1; mouse genomic designation, Titf1) (20). Mutagenesis of the NFI sites greatly diminished SP-C promoter activity in transient transfection experiments in mouse lung epithelial cells and blocked NFI-Amediated activation of the SP-C promoter in HeLa cells (3). Whether NFI affects SP-C promoter activity in vivo is not known.Isoforms of NFI arise from differential splicing of the gene products from the four NFI genes, Nfia, Nfib, Nfic, and Nfix. Although NFI is sometimes thought to be a ubiquitous transcription factor, these genes are expressed in specific overlapping patterns during fetal development and at lower levels in specific tissues in the adult (10). The relative expression levels of the four NFI genes vary with cell type, cell cycle, and differentiation status (16). Mice homozygous for deletion of Nfib die at birth from respiratory distress due to a block in lung maturation, suggesting that this NFI family member is required for late-fetal or perinatal lung development (18).NFI family members are highly homologous in the aminoterminal DNA binding and dimerization domain but are divergent in the carboxyl-terminal transactivation-repression domain (1, 24; reviewed in reference 17). Further diversity of the transactivation domain is accomplished by alternative splicing that creates regions of variable proline richness. The significance of the proline-rich areas is not understood but they may form sites of protein-protein interaction. To test the hypothesis that changes in the repertoire of NFI family members directly modulate transcription of the SP-C gene, we measured promoter activation by selected isoforms of each of the NFI genes, alone and in combination with one another and TTF-1.TTF-1 is a homeodomain-containing transcription factor that regulates morphogenesis and differential gene expression in the lung, thyroid, and ventral forebrain. Mice lacking TTF-1 protein do not undergo proper lung or thyroid differentiation and die at birth from respiratory distress (21). TTF-1 is expressed in the pulmonary epithelium during development and regulates the expression of the surfactant protein genes (reviewed in reference 42). TTF-1 interacts with retinoic acid receptor alpha (RAR␣) and TIF2 by mammalian two-hybrid analysis and synergistically interacts with R...

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Objectives: To observe levels of matrix metalloproteinase (MMP)-9 and evaluate their significance in various stages of idiopathic atrial fibrillation (AF). Methods: Patients with idiopathic AF were recruited into this prospective study and classified into one of three groups according to stage of disease progression: paroxysmal AF; persistent AF; permanent AF. Healthy individuals were enrolled as control subjects. Serum levels of MMP-9 in all four groups were determined using a double-antibody sandwich enzyme-linked immunosorbent assay. Results: Each AF group included 25 patients; 40 healthy individuals were included as controls. MMP-9 levels in the three AF groups were significantly higher than in the control group: 168.72 AE 25.970, 201.36 AE 31.26 and 253.20 AE 22.99 ng/ml for the paroxysmal, persistent and permanent AF groups respectively, versus 76.80 AE 14.90 ng/ml for the control group. MMP-9 levels increased with idiopathic AF disease progression (P < 0.05). Conclusions: An elevated MMP-9 level appears to be associated with a diagnosis of AF. MMP-9 levels appear to increase in relation to the stage of idiopathic AF progression.