The molecular mechanisms underlying the acquisition of resistance to the antiestrogen Faslodex are poorly understood, although enhanced expression and activity of nuclear factor KB (NFKB) have been implicated as a critical element of this phenotype. The purpose of this study was to elucidate the mechanism by which NFKB up-regulation contributes to Faslodex resistance and to determine whether ph...

Although p120-catenin regulates adherens junction (AJ) stability in cultured cells, genetic studies in lower eukaryotes have not revealed a role for this protein in vivo. Using conditional targeting in mice, we show that p120 null neonatal epidermis exhibits reduced intercellular AJ components but no overt disruption in barrier function or intercellular adhesion. As the mice age, however, they ...

The human body is constantly challenged by a variety of commensal and pathogenic microorganisms that trigger the immune system. Central in the first line of defence is the patternrecognition receptor (PRR)-induced stimulation of the NFkB pathway, leading to NFkB activation. The subsequent production of pro-inflammatory cytokines and/or antimicrobial peptides results in recruitment of profession...

Excitotoxin-induced destruction of striatal neurons, proposed as a model of Huntington’s disease, involves a process having the biochemical stigmata of apoptosis. Recent studies suggested that transcription factor nuclear factor (NF)-kB may be involved in excitotoxicity. To further analyze the contribution of NFkB to excitotoxic neuronal death in vivo, changes in binding activities of NFkB and ...

Oxidized low density lipoprotein (oxLDL) is known to alter the expression of inflammatory gene products in mononuclear phagocytes. The mechanisms involved in this effect were studied by examining the activation of nuclear factor kB (NFkB), a transcription factor known to be important in controlling the expression of such genes. Pretreatment of peritoneal macrophages with oxLDL modulated the act...

Four out of five patients diagnosed with esophageal squamous cell carcinoma (ESCC) will die within five years. This is primarily a result of the aggressive invasive potential of the disease. Our research is focused on the interplay between tumor suppressors and oncogenes in the invasive process. Specifically, EGFR and p120-catenin (p120ctn) are commonly dysregulated genes that are indicative of...

Neuroblastoma resistance to apoptosis may contribute to the aggressive behavior of this tumor. Therefore, it would be relevant to activate endogenous cellular death mechanisms as a way to improve neuroblastoma therapy. We used the neuroblastoma SH-SY5Y cell line as a model to study the mechanisms involved in acetaminophen (AAP)-mediated toxicity by measuring CYP2E1 enzymatic activity, NFkB p65 ...

The microenvironment of cells controls their phenotype, and thereby the architecture of the emerging multicellular structure or tissue. We have reported more than a dozen microenvironmental factors whose signaling must be integrated in order to effect an organized, functional tissue morphology. However, the factors that prevent integration of signaling pathways that merge form and function are ...

The elemental physiology of the highly complex and regulated cellular response to stress remains poorly understood. Hypothermia and reperfusion are necessary and unavoidable stresses associated with the procurement, storage and transplantation of organs such as the kidney. Signal transduction pathways and transcription factors are evolutionarily conserved mediators of stress responses. This pro...

Immune responses must be well restrained in a steady state to avoid excessive inflammation. However, such restraints are quickly removed to exert antimicrobial responses. Here we report a role of autophagy in an early host antifungal response by enhancing NFkB activity through A20 sequestration. Enhancement of NFkB activation is achieved by autophagic depletion of A20, an NFkB inhibitor, in F4/...