Altered expression of helix-loop-helix transcriptional regulators and cyclin D1 in Wnt-1-transformed PC12 cells.
Nerve growth factor induces PC12 cells to differentiate from a chromaffin cell to a sympathetic neuronal phenotype. In contrast, PC12 cells, which stably express Wnt-1, a secreted signaling factor required for development of mammalian midbrain and cerebellum, fail to express differentiation-specific genes in response to nerve growth factor. Analysis of factors binding to E box-containing regulatory elements of the terminal differentiation gene encoding peripherin suggested a differentiation-specific control of expression of helix-loop-helix transcriptional regulators. Specifically, the MASH-1 (mammalian achaete-scute homologue) helix-loop-helix transcription factor, which plays a positive role in neuronal differentiation, is reduced in Wnt-1/PC12 cells, and HES-1, a negative regulator of MASH-1, is increased. These data suggest that the differentiation block may result from induction of HES-1. Wnt-1/PC12 cells also proliferate more rapidly and express increased levels of cyclin D1. Thus, Wnt-1 may block the differentiation and enhance the proliferation of PC12 cells by activating HES-1 and cyclin D1 and repressing MASH-1.
Issack
P S
PS
Howard Hughes Medical Institute, Department of Biochemistry and Kaplan Cancer Center, New York University Medical Center, New York 10016, USA.
Ziff
E B
EB
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D002454:Cell Differentiation; D002455:Cell Division; D002461:Cell Line, Transformed; D019938:Cyclin D1 / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005786:Gene Expression Regulation; D018257:Helix-Loop-Helix Motifs; D018398:Homeodomain Proteins / Q000235:genetics*; D007381:Intermediate Filament Proteins / Q000235:genetics; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins / Q000235:genetics; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D016716:PC12 Cells; D064531:Peripherins; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000502:physiology; D051381:Rats; D000072056:Transcription Factor HES-1; D014157:Transcription Factors / Q000235:genetics*; D014170:Transformation, Genetic; D051153:Wnt Proteins; D051155:Wnt1 Protein; D029961:Zebrafish Proteins
D051792:Basic Helix-Loop-Helix Proteins; D019938:Cyclin D1; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D007381:Intermediate Filament Proteins; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D064531:Peripherins; D011518:Proto-Oncogene Proteins; D000072056:Transcription Factor HES-1; D014157:Transcription Factors; D051153:Wnt Proteins; D051155:Wnt1 Protein; D029961:Zebrafish Proteins; C499318:Ascl1 protein, rat; C489735:Hes1 protein, rat; C495245:Wnt1 protein, rat