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We investigated whether lysophosphatidylethanolamine (LPE) modulates cellular signaling in different cell types. SK-OV3 ovarian cancer cells and OVCAR-3 ovarian cancer cells were responsive to LPE. LPE-stimulated intracellular calcium concentration ([Ca 2+ ] i ) increase was inhibited by U-73122, suggesting that LPE stimulates calcium signaling via phospholipase C activation. Moreover, pertussis toxin (PTX) almost completely inhibited [Ca 2+ ] i increase by LPE, indicating the involvement of PTX-sensitive G-proteins. Furthermore, we found that LPE stimulated chemotactic migration and cellular invasion in SK-OV3 ovarian cancer cells. We examined the role of lysophosphatidic acid receptors on LPE-stimulated cellular responses using HepG2 cells transfected with different LPA receptors, and found that LPE failed to stimulate nuclear factor kappa B-driven luciferase. We suggest that LPE stimulates a membrane bound receptor, different from well known LPA receptors, resulting in chemotactic migration and cellular invasion in SK-OV3 ovarian cancer cells.

The dual-specificity tyrosine(Y)-phosphorylation-regulated kinase 1A (Dyrk1A) gene is located on human chromosome 21 and encodes a proline-directed protein kinase that might be responsible for mental retardation and early onset of Alzheimer's disease (AD) in Down syndrome (DS) patients. Presenilin 1 (PS1) is a key component of the c-secretase complex in the generation of b-amyloid (Ab), an important trigger protein in the pathogenesis of AD. Increased Dyrk1A expression has been reported in human AD and DS brains. We previously showed that Dyrk1A increased Ab production in mammalian cells and transgenic mice that over-express Dyrk1A. In this study, we describe a potential mechanism by which Ab is increased in Dyrk1A-over-expressing DS and AD brains. First, we show that PS1 is phosphorylated by the Dyrk1A at Thr 354 and that this phosphorylation increases c-secretase activity. Then, using transgenic mice that over-express human Dyrk1A, we demonstrate that phospho-Thr354-PS1 (pT354-PS1) expression is enhanced when Dyrk1A level is increased. We also show that pT354-PS1 is more stable than the unphosphorylated form of PS1. These results reveal a potential regulatory link between Dyrk1A and PS1 in the Ab pathway of DS and AD brains, suggesting that up-regulated Dyrk1A may accelerate AD pathogenesis through PS1 phosphorylation.

Lung cancer is the leading cause of cancer deaths worldwide. Recent advances in targeted therapies hold promise for the development of new treatments for certain subsets of cancer patients by targeting specific signaling molecule. Based on the identification of the transcription factor cyclic AMP response element-binding protein (CREB) as an important regulator of growth of several types of cancers and our recent findings of its importance in normal differentiation of bronchial epithelial cells, we hypothesized that CREB plays an important pathobiologic role in lung carcinogenesis. We conducted this initial study to determine whether the expression and activation status of CREB are altered in non-small cell lung cancer (NSCLC) and of any prognostic importance in NSCLC patients. We found that the expression levels of mRNA and protein of CREB and phosphorylated CREB (p-CREB) were significantly higher in most of the NSCLC cell lines and tumor specimens than in the normal human tracheobronchial epithelial cells and adjacent normal lung tissue, respectively. Analysis of CREB mRNA expression and the CREB gene copy number showed that CREB overexpression occurred mainly at the transcriptional level. Immunohistochemical analysis of tissue microarray slides containing sections of NSCLC specimens obtained from 310 patients showed that a decreased survival duration was significantly associated with overexpression of CREB or p-CREB in never smokers but not in current or former smokers with NSCLC. These are the first reported results illustrating the potential of CREB as a molecular target for the prevention and treatment of NSCLC, especially in never smokers. [Cancer Res 2008;68(15):6065-73]

Purpose -The purpose of this paper is to explore how the facial expression of the reviewer's avatar interacts with the valence of the consumer review to influence consumer purchase decisions. Design/methodology/approach -A 2 (facial expression of the reviewer's avatar) Â 2 (valence of the consumer review) between-subjects online experimental design was used. Findings -It was found that when the consumer review was positive, participants exposed to the reviewer's angry-looking avatar were more likely to attribute the review to the product's performance than those exposed to the happy-looking avatar. The causal attribution toward product performance, in turn, influenced the strength of intention to purchase the brand positively. When the consumer review was negative, however, there were no differential effects between the happy-looking and the angry-looking avatars. Originality/value -This study contributes to the literature on consumer reviews by identifying an important source characteristic that consumers consider when processing consumer reviews -the facial expression of the reviewer's avatar.

Purpose -The purpose of this paper is to investigate how the source of brand-related user-generated content (UGC) (a close friend vs a celebrity) interacts with content sponsorship (organic UGC vs sponsored UGC) to influence consumer causal attributions, brand attitude, and intention to comply with the recommendation. Design/methodology/approach -In all, 285 college students participated in a two (source: a close friend vs a celebrity) by two (content sponsorship: organic vs sponsored) between-subjects online experimental design. Findings -Results showed that recommendation from a close friend generated more information-sharing attributions and less monetary-gain attributions than did recommendation from a celebrity when the brandrelated UGC was organic. In contrast, source type did not influence causal attributions differently when the UGC was sponsored. Further, this study demonstrated that both information-sharing and monetary-gain attributions mediated the effects of source type and content sponsorship on brand attitude and intention to comply with the recommendation. Originality/value -This study is one of the first to examine the effectiveness of celebrities as a source of brand-related UGC. Also, this research extends the existing knowledge about source effects by examining the relative effectiveness of two sources of product information, close friends and celebrities, who have both been found to be individually effective in the traditional marketing context. Additionally, the findings of this study that the relative effectiveness of source type depends on whether brand-related UGC is sponsored or not add a further insight into how source type influences the effectiveness of brand-related UGC.