Regulation of cyclooxygenase-2 and periostin by Wnt-3 in mouse mammary epithelial cells.
Wnt family members are critical in developmental processes and have been shown to promote carcinogenesis when ectopically expressed in the mouse mammary gland. The gene expression pattern mediated by Wnt is pivotal for these diverse responses. The Wnt pathway has been conserved among different species. Genetic studies have shown that Wnt effects are mediated, at least in part, by beta-catenin, which regulates transcription of "downstream genes." Wnt stimulation inactivates glycogen-synthase kinase-3beta (GSK-3) with subsequent stabilization of beta-catenin, which after heterodimerizing with lymphocyte enhancer factor-1/T-cell factor cofactors stimulates transcription. To establish whether Wnt-stimulated transcription is mediated solely by beta-catenin, a comparison was made of gene expression profiles in response to Wnt-3, overexpression of beta-catenin, and inhibition of GSK-3. Infection of cells with Wnt-3 and inhibition of GSK-3 regulate a set of genes that include cyclooxygenase-2 and periostin. Interestingly, overexpression of beta-catenin or reducing beta-catenin levels with antisense oligonucleotide transfection did not have any effect on cyclooxygenase-2 or periostin expression, thereby defining a Wnt pathway, which cannot be mimicked by beta-catenin overexpression.
Haertel-Wiesmann
M
M
Chiron Corporation, Emeryville, California 94608, USA.
Liang
Y
Y
Fantl
W J
WJ
Williams
L T
LT
D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000235:genetics*; D002460:Cell Line; D051546:Cyclooxygenase 2; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D017930:Genes, Reporter / Q000235:genetics; D038362:Glycogen Synthase Kinase 3; D038341:Glycogen Synthase Kinases; D007527:Isoenzymes / Q000235:genetics* / Q000378:metabolism; D018021:Lithium Chloride / Q000494:pharmacology; D008321:Mammary Glands, Animal / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D051379:Mice; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics* / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D015534:Trans-Activators; D051153:Wnt Proteins; D060508:Wnt3 Protein; D051176:beta Catenin
C495267:CTNNB1 protein, mouse; D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; D007527:Isoenzymes; D016376:Oligonucleotides, Antisense; C082838:Postn protein, mouse; D011506:Proteins; D012333:RNA, Messenger; D015534:Trans-Activators; D051153:Wnt Proteins; D060508:Wnt3 Protein; C555508:Wnt3 protein, mouse; D051176:beta Catenin; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D038341:Glycogen Synthase Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D038362:Glycogen Synthase Kinase 3; D018021:Lithium Chloride; D015232:Dinoprostone