Interaction between vascular cell adhesion molecule 1 (VCAM-1), which appears on the surface of endothelial cells in response to inflammation, and its integrin counter receptor, a4fi1, on immune cells is responsible for targeting these immune cells to cytokine-stimulated endothelium. In addition to its role in the immune system, VCAM-1 is also expressed in a developmentally specific pattern on differentiating skeletal muscle, where it mediates cell-cell interactions important for myogenesis through interaction with a4f31. In contrast to endothelium, there is high basal expression of VCAM-1 in skeletal muscle cells and the expression is not cytokine-responsive. Here, we examine the molecular basis for these contrasting patterns of expression in muscle and endothelium, using VCAM-1 promoter constructs in a series of transfection assays. In endothelial cells, octamer binding sites act as silencers that prevent VCAM-1 expression in unstimulated cells. Tumor necrosis factor a overcomes the negative effects of these octamers and activates the promoter through two adjacent NF-KB binding sites. In muscle cells, a positionspecific enhancer located between bp -21 and -5 overrides the effect of other promoter elements, resulting in constitutive VCAM-1 expression. A nuclear protein binds the positionspecific enhancer in muscle but not endothelial cells; thus the pattern of expression of this protein could control enhancer activity.

No abstract

No abstract

Effective chemoprevention of lung cancer in high-risk patients through the administration of pharmacologic or nutritional agents is urgently needed. Aerosol inhalation can deliver chemopreventive agents directly to the respiratory tract to inhibit the tumorigenic process. In this study, polyphenon E (PolyE) and (-)-epigallocatechin-3-gallate (EGCG) were administered by aerosol delivery to A/J mice beginning 2 weeks after carcinogen treatment and continuing daily by inhalation throughout the remainder of the study (20 weeks). PolyE decreased tumor load by approximately 59%. However, EGCG, both at the same dose and at a higher dose, failed to inhibit lung carcinogenesis. These results indicate that aerosol delivery of PolyE, but not EGCG, may be a useful chemopreventive protocol in subjects at high risk for lung cancer.

No abstract