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Full-Text Articles in Medicine and Health Sciences

Eliciting The Low-Activity Aldehyde Dehydrogenase Asian Phenotype By An Antisense Mechanism Results In An Aversion To Ethanol., E Garver, Tu Gc, Q N Cao, M Aini, F Zhou, Y Israel Sep 2001

Eliciting The Low-Activity Aldehyde Dehydrogenase Asian Phenotype By An Antisense Mechanism Results In An Aversion To Ethanol., E Garver, Tu Gc, Q N Cao, M Aini, F Zhou, Y Israel

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

A mutation in the gene encoding for the liver mitochondrial aldehyde dehydrogenase (ALDH2-2), present in some Asian populations, lowers or abolishes the activity of this enzyme and results in elevations in blood acetaldehyde upon ethanol consumption, a phenotype that greatly protects against alcohol abuse and alcoholism. We have determined whether the administration of antisense phosphorothioate oligonucleotides (ASOs) can mimic the low-activity ALDH2-2 Asian phenotype. Rat hepatoma cells incubated for 24 h with an antisense oligonucleotide (ASO-9) showed reductions in ALDH2 mRNA levels of 85% and ALDH2 (half-life of 22 h) activity of 55% equivalent to a >90% inhibition in ALDH2 …


Induction Of Beta3-Integrin Gene Expression By Sustained Activation Of The Ras-Regulated Raf-Mek-Extracellular Signal-Regulated Kinase Signaling Pathway., Douglas Woods, Holly Cherwinski, Eleni Venetsanakos, Arun Bhat, Stephan Gysin, Martine Humbert, Paul F. Bray, Vicki L. Saylor, Martin Mcmahon May 2001

Induction Of Beta3-Integrin Gene Expression By Sustained Activation Of The Ras-Regulated Raf-Mek-Extracellular Signal-Regulated Kinase Signaling Pathway., Douglas Woods, Holly Cherwinski, Eleni Venetsanakos, Arun Bhat, Stephan Gysin, Martine Humbert, Paul F. Bray, Vicki L. Saylor, Martin Mcmahon

Cardeza Foundation for Hematologic Research

Alterations in the expression of integrin receptors for extracellular matrix (ECM) proteins are strongly associated with the acquisition of invasive and/or metastatic properties by human cancer cells. Despite this, comparatively little is known of the biochemical mechanisms that regulate the expression of integrin genes in cells. Here we demonstrate that the Ras-activated Raf-MEK-extracellular signal-regulated kinase (ERK) signaling pathway can specifically control the expression of individual integrin subunits in a variety of human and mouse cell lines. Pharmacological inhibition of MEK1 in a number of human melanoma and pancreatic carcinoma cell lines led to reduced cell surface expression of alpha6- and …