Wnt-1 inhibits nerve growth factor-induced differentiation of PC12 cells by preventing the induction of some but not all late-response genes.
The vertebrate Wnt-1 proto-oncogene is expressed transiently in embryonic brain and functions in the development of the central nervous system and neural crest. The role of Wnt-1 in neural crest development appears to be to increase the number of certain progenitor cells by preventing their premature differentiation. To study the mechanism by which this transient Wnt-1 expression inhibits differentiation we have constructed PC12 pheochromocytoma cells in which Wnt-1 expression levels were controlled by use of a tetracycline-responsive transactivator. Induction of Wnt-1 expression by tetracycline withdrawal was followed by activation of the Wnt-1 signalling pathway as shown by activation of the Lef-1/Tcf transcription factor. Wnt-1 expression by these cells resulted in reversible inhibition of NGF-induced neurite outgrowth, but it did not adversely affect the maintenance of previously formed NGF-induced neurites. Wnt-1 expression also partially blocked the ability of NGF to decrease the rate of cell multiplication. Wnt-1 decreased the NGF-induced expression of the late-response gene SCG10 but not of the immediate early genes, fos, Nur77 and UPAR (urokinase-type plasminogen activator receptor) nor of the late-response genes GAP-43 and collagenase. The Wnt-1 expressing PC12 cells multiplied at a greater rate when they expressed Wnt-1 than they did in the absence of Wnt-1 expression, a result that is consistent with the proposal that Wnt-1 may also act as a mitogen.
Chou
A H
AH
Department of Biological Chemistry, UCLA Medical School, University of California, 90095, Los Angeles, CA 90095, USA.
Zheng
S
S
Itsukaichi
T
T
Howard
B D
BD
D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D027322:Amino Acid Transport System X-AG; D000818:Animals; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000378:metabolism; D051157:Frizzled Receptors; D019922:GAP-43 Protein / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D017781:Genes, Immediate-Early / Q000235:genetics; D018698:Glutamic Acid / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D051821:Lymphoid Enhancer-Binding Factor 1; D008565:Membrane Proteins; D051379:Mice; D008868:Microtubule Proteins; D020932:Nerve Growth Factor / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D009414:Nerve Growth Factors / Q000235:genetics; D016501:Neurites / Q000187:drug effects / Q000378:metabolism*; D016716:PC12 Cells; D011506:Proteins / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011956:Receptors, Cell Surface / Q000235:genetics; D055293:Receptors, Urokinase Plasminogen Activator; D015398:Signal Transduction / Q000187:drug effects; D050777:Stathmin; D013752:Tetracycline / Q000494:pharmacology; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects / Q000235:genetics; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics; D051153:Wnt Proteins; D051155:Wnt1 Protein; D029961:Zebrafish Proteins
D018528:ATP-Binding Cassette Transporters; D027322:Amino Acid Transport System X-AG; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D051157:Frizzled Receptors; D019922:GAP-43 Protein; D047908:Intracellular Signaling Peptides and Proteins; C497574:Lef1 protein, mouse; C497575:Lef1 protein, rat; D051821:Lymphoid Enhancer-Binding Factor 1; D008565:Membrane Proteins; D008868:Microtubule Proteins; D009414:Nerve Growth Factors; C524899:Plaur protein, mouse; C524900:Plaur protein, rat; D011506:Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D050777:Stathmin; C512849:Stmn2 protein, mouse; C512848:Stmn2 protein, rat; D014157:Transcription Factors; D051153:Wnt Proteins; D051155:Wnt1 Protein; C495246:Wnt1 protein, mouse; C495245:Wnt1 protein, rat; D029961:Zebrafish Proteins; D018698:Glutamic Acid; D020932:Nerve Growth Factor; D014446:Tyrosine 3-Monooxygenase; D013752:Tetracycline