[Small non-coding RNAs: new targets and new therapeutic possibilities].

The discovery of regulatory small non-coding RNAs represents a revolution in our understanding of gene regulation. These small non-coding RNAs are powerful tools for exploring cellular pathways and for artificially controlling gene expression. Natural small RNAs also represent potential therapeutic targets.

Distinctive role of integrin-mediated adhesion in TNF-induced PKB/Akt and NF-kappaB activation and endothelial cell survival.

Tumor necrosis factor (TNF) is a pro-inflammatory cytokine exerting pleiotropic effects on endothelial cells. Depending on the vascular context it can induce endothelial cell activation and survival or death. The microenvironmental cues determining whether endothelial cells will survive or die, however, have remained elusive.

A role for AP-1 in apoptosis: the case for and against.

The nuclear transcription factor AP-1, composed of dimers of Fos and Jun proteins, has been linked to a startling breadth of cellular events including cell transformation, proliferation, differentiation and apoptosis. AP-1 is often portrayed as a general, nuclear decision-maker that determines life or death cell fates in response to extracellular stimuli. However, it is increasingly clear that the cellular context is critical for determining the contribution of AP-1 to cellular fates, and the role of AP-1 in apoptosis should be considered within the context of a complex network of nuclear factors that respond simultaneously to a wide range of signal transduction pathways.

Role of Fas and granule exocytosis pathways in tumor-infiltrating T lymphocyte-induced apoptosis of autologous human lung-carcinoma cells.

We have isolated a cytotoxic T lymphocyte (CTL) clone, Heu161, that reacts specifically with the human autologous lung carcinoma cell line IGR-Heu. We first demonstrated that IGR-Heu lacked Fas-receptor expression and was resistant to CD95-induced apoptosis. To further elucidate the role of Fas in tumor immune surveillance, we have stably transfected IGR-Heu with a Fas-expression vector and isolated CD95-sensitive and -resistant clones.

Effect of nuclear factor kappaB inhibition on tumor cell sensitivity to natural killer-mediated cytolytic function.

Inhibition of the transcription factor NF-kappaB has been reported to increase cell sensitivity to TNF and some cytotoxic drugs. We investigated the effect of NK-kappaB inhibition on the susceptibility of tumor cells to freshly isolated, nonactivated, human NK cells and to a TCRgamma/delta T cell clone displaying an MHC-unrestricted "NK-like" lysis. Using electrophoretic mobility shift assay, we first demonstrated that NF-kappaB/DNA binding activity was induced in target cells following coculture with NK cells or TCRgamma/delta T cell clone.