Cargando…
The Forkhead Transcription Factor FOXP2 Is Required for Regulation of p21(WAF1/CIP1) in 143B Osteosarcoma Cell Growth Arrest
Mutations of the forkhead transcription factor FOXP2 gene have been implicated in inherited speech-and-language disorders, and specific Foxp2 expression patterns in neuronal populations and neuronal phenotypes arising from Foxp2 disruption have been described. However, molecular functions of FOXP2 a...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2015
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4452790/ https://www.ncbi.nlm.nih.gov/pubmed/26034982 http://dx.doi.org/10.1371/journal.pone.0128513 |
_version_ | 1782374364072640512 |
---|---|
author | Gascoyne, Duncan M. Spearman, Hayley Lyne, Linden Puliyadi, Rathi Perez-Alcantara, Marta Coulton, Les Fisher, Simon E. Croucher, Peter I. Banham, Alison H. |
author_facet | Gascoyne, Duncan M. Spearman, Hayley Lyne, Linden Puliyadi, Rathi Perez-Alcantara, Marta Coulton, Les Fisher, Simon E. Croucher, Peter I. Banham, Alison H. |
author_sort | Gascoyne, Duncan M. |
collection | PubMed |
description | Mutations of the forkhead transcription factor FOXP2 gene have been implicated in inherited speech-and-language disorders, and specific Foxp2 expression patterns in neuronal populations and neuronal phenotypes arising from Foxp2 disruption have been described. However, molecular functions of FOXP2 are not completely understood. Here we report a requirement for FOXP2 in growth arrest of the osteosarcoma cell line 143B. We observed endogenous expression of this transcription factor both transiently in normally developing murine osteoblasts and constitutively in human SAOS-2 osteosarcoma cells blocked in early osteoblast development. Critically, we demonstrate that in 143B osteosarcoma cells with minimal endogenous expression, FOXP2 induced by growth arrest is required for up-regulation of p21(WAF1/CIP1). Upon growth factor withdrawal, FOXP2 induction occurs rapidly and precedes p21(WAF1/CIP1) activation. Additionally, FOXP2 expression could be induced by MAPK pathway inhibition in growth-arrested 143B cells, but not in traditional cell line models of osteoblast differentiation (MG-63, C2C12, MC3T3-E1). Our data are consistent with a model in which transient upregulation of Foxp2 in pre-osteoblast mesenchymal cells regulates a p21-dependent growth arrest checkpoint, which may have implications for normal mesenchymal and osteosarcoma biology. |
format | Online Article Text |
id | pubmed-4452790 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-44527902015-06-09 The Forkhead Transcription Factor FOXP2 Is Required for Regulation of p21(WAF1/CIP1) in 143B Osteosarcoma Cell Growth Arrest Gascoyne, Duncan M. Spearman, Hayley Lyne, Linden Puliyadi, Rathi Perez-Alcantara, Marta Coulton, Les Fisher, Simon E. Croucher, Peter I. Banham, Alison H. PLoS One Research Article Mutations of the forkhead transcription factor FOXP2 gene have been implicated in inherited speech-and-language disorders, and specific Foxp2 expression patterns in neuronal populations and neuronal phenotypes arising from Foxp2 disruption have been described. However, molecular functions of FOXP2 are not completely understood. Here we report a requirement for FOXP2 in growth arrest of the osteosarcoma cell line 143B. We observed endogenous expression of this transcription factor both transiently in normally developing murine osteoblasts and constitutively in human SAOS-2 osteosarcoma cells blocked in early osteoblast development. Critically, we demonstrate that in 143B osteosarcoma cells with minimal endogenous expression, FOXP2 induced by growth arrest is required for up-regulation of p21(WAF1/CIP1). Upon growth factor withdrawal, FOXP2 induction occurs rapidly and precedes p21(WAF1/CIP1) activation. Additionally, FOXP2 expression could be induced by MAPK pathway inhibition in growth-arrested 143B cells, but not in traditional cell line models of osteoblast differentiation (MG-63, C2C12, MC3T3-E1). Our data are consistent with a model in which transient upregulation of Foxp2 in pre-osteoblast mesenchymal cells regulates a p21-dependent growth arrest checkpoint, which may have implications for normal mesenchymal and osteosarcoma biology. Public Library of Science 2015-06-02 /pmc/articles/PMC4452790/ /pubmed/26034982 http://dx.doi.org/10.1371/journal.pone.0128513 Text en © 2015 Gascoyne et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Gascoyne, Duncan M. Spearman, Hayley Lyne, Linden Puliyadi, Rathi Perez-Alcantara, Marta Coulton, Les Fisher, Simon E. Croucher, Peter I. Banham, Alison H. The Forkhead Transcription Factor FOXP2 Is Required for Regulation of p21(WAF1/CIP1) in 143B Osteosarcoma Cell Growth Arrest |
title | The Forkhead Transcription Factor FOXP2 Is Required for Regulation of p21(WAF1/CIP1) in 143B Osteosarcoma Cell Growth Arrest |
title_full | The Forkhead Transcription Factor FOXP2 Is Required for Regulation of p21(WAF1/CIP1) in 143B Osteosarcoma Cell Growth Arrest |
title_fullStr | The Forkhead Transcription Factor FOXP2 Is Required for Regulation of p21(WAF1/CIP1) in 143B Osteosarcoma Cell Growth Arrest |
title_full_unstemmed | The Forkhead Transcription Factor FOXP2 Is Required for Regulation of p21(WAF1/CIP1) in 143B Osteosarcoma Cell Growth Arrest |
title_short | The Forkhead Transcription Factor FOXP2 Is Required for Regulation of p21(WAF1/CIP1) in 143B Osteosarcoma Cell Growth Arrest |
title_sort | forkhead transcription factor foxp2 is required for regulation of p21(waf1/cip1) in 143b osteosarcoma cell growth arrest |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4452790/ https://www.ncbi.nlm.nih.gov/pubmed/26034982 http://dx.doi.org/10.1371/journal.pone.0128513 |
work_keys_str_mv | AT gascoyneduncanm theforkheadtranscriptionfactorfoxp2isrequiredforregulationofp21waf1cip1in143bosteosarcomacellgrowtharrest AT spearmanhayley theforkheadtranscriptionfactorfoxp2isrequiredforregulationofp21waf1cip1in143bosteosarcomacellgrowtharrest AT lynelinden theforkheadtranscriptionfactorfoxp2isrequiredforregulationofp21waf1cip1in143bosteosarcomacellgrowtharrest AT puliyadirathi theforkheadtranscriptionfactorfoxp2isrequiredforregulationofp21waf1cip1in143bosteosarcomacellgrowtharrest AT perezalcantaramarta theforkheadtranscriptionfactorfoxp2isrequiredforregulationofp21waf1cip1in143bosteosarcomacellgrowtharrest AT coultonles theforkheadtranscriptionfactorfoxp2isrequiredforregulationofp21waf1cip1in143bosteosarcomacellgrowtharrest AT fishersimone theforkheadtranscriptionfactorfoxp2isrequiredforregulationofp21waf1cip1in143bosteosarcomacellgrowtharrest AT croucherpeteri theforkheadtranscriptionfactorfoxp2isrequiredforregulationofp21waf1cip1in143bosteosarcomacellgrowtharrest AT banhamalisonh theforkheadtranscriptionfactorfoxp2isrequiredforregulationofp21waf1cip1in143bosteosarcomacellgrowtharrest AT gascoyneduncanm forkheadtranscriptionfactorfoxp2isrequiredforregulationofp21waf1cip1in143bosteosarcomacellgrowtharrest AT spearmanhayley forkheadtranscriptionfactorfoxp2isrequiredforregulationofp21waf1cip1in143bosteosarcomacellgrowtharrest AT lynelinden forkheadtranscriptionfactorfoxp2isrequiredforregulationofp21waf1cip1in143bosteosarcomacellgrowtharrest AT puliyadirathi forkheadtranscriptionfactorfoxp2isrequiredforregulationofp21waf1cip1in143bosteosarcomacellgrowtharrest AT perezalcantaramarta forkheadtranscriptionfactorfoxp2isrequiredforregulationofp21waf1cip1in143bosteosarcomacellgrowtharrest AT coultonles forkheadtranscriptionfactorfoxp2isrequiredforregulationofp21waf1cip1in143bosteosarcomacellgrowtharrest AT fishersimone forkheadtranscriptionfactorfoxp2isrequiredforregulationofp21waf1cip1in143bosteosarcomacellgrowtharrest AT croucherpeteri forkheadtranscriptionfactorfoxp2isrequiredforregulationofp21waf1cip1in143bosteosarcomacellgrowtharrest AT banhamalisonh forkheadtranscriptionfactorfoxp2isrequiredforregulationofp21waf1cip1in143bosteosarcomacellgrowtharrest |