The forkhead transcription factor FOXP2 is required for regulation of p21WAF1/CIP1 in 143B osteosarcoma cell growth arrest
Mutations of the forkhead transcription factor <em>FOXP2</em> gene have been implicated in inherited speech-and-language disorders, and specific Foxp2 expression patterns in neuronal populations and neuronal phenotypes arising from <em>Foxp2</em> disruption have been describe...
| Main Authors: | , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Public Library of Science
2015
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| _version_ | 1797109927854997504 |
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| author | Gascoyne, DM Spearman, H Lyne, L Puliyadi, R Perez-Alcantara, M Coulton, L Fisher, SE Croucher, PI Banham, AH |
| author_facet | Gascoyne, DM Spearman, H Lyne, L Puliyadi, R Perez-Alcantara, M Coulton, L Fisher, SE Croucher, PI Banham, AH |
| author_sort | Gascoyne, DM |
| collection | OXFORD |
| description | Mutations of the forkhead transcription factor <em>FOXP2</em> gene have been implicated in inherited speech-and-language disorders, and specific Foxp2 expression patterns in neuronal populations and neuronal phenotypes arising from <em>Foxp2</em> 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 <em>p21<sup>WAF1/CIP1</sup></em>. Upon growth factor withdrawal, FOXP2 induction occurs rapidly and precedes <em>p21<sup>WAF1/CIP1</sup></em> 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. |
| first_indexed | 2024-03-07T07:48:03Z |
| format | Journal article |
| id | oxford-uuid:26b05f7e-9b53-4d8b-ac4c-8d75afb21391 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T07:48:03Z |
| publishDate | 2015 |
| publisher | Public Library of Science |
| record_format | dspace |
| spelling | oxford-uuid:26b05f7e-9b53-4d8b-ac4c-8d75afb213912023-06-23T16:36:03ZThe forkhead transcription factor FOXP2 is required for regulation of p21WAF1/CIP1 in 143B osteosarcoma cell growth arrestJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:26b05f7e-9b53-4d8b-ac4c-8d75afb21391EnglishORA DepositPublic Library of Science2015Gascoyne, DMSpearman, HLyne, LPuliyadi, RPerez-Alcantara, MCoulton, LFisher, SECroucher, PIBanham, AHMutations of the forkhead transcription factor <em>FOXP2</em> gene have been implicated in inherited speech-and-language disorders, and specific Foxp2 expression patterns in neuronal populations and neuronal phenotypes arising from <em>Foxp2</em> 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 <em>p21<sup>WAF1/CIP1</sup></em>. Upon growth factor withdrawal, FOXP2 induction occurs rapidly and precedes <em>p21<sup>WAF1/CIP1</sup></em> 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. |
| spellingShingle | Gascoyne, DM Spearman, H Lyne, L Puliyadi, R Perez-Alcantara, M Coulton, L Fisher, SE Croucher, PI Banham, AH The forkhead transcription factor FOXP2 is required for regulation of p21WAF1/CIP1 in 143B osteosarcoma cell growth arrest |
| title | The forkhead transcription factor FOXP2 is required for regulation of p21WAF1/CIP1 in 143B osteosarcoma cell growth arrest |
| title_full | The forkhead transcription factor FOXP2 is required for regulation of p21WAF1/CIP1 in 143B osteosarcoma cell growth arrest |
| title_fullStr | The forkhead transcription factor FOXP2 is required for regulation of p21WAF1/CIP1 in 143B osteosarcoma cell growth arrest |
| title_full_unstemmed | The forkhead transcription factor FOXP2 is required for regulation of p21WAF1/CIP1 in 143B osteosarcoma cell growth arrest |
| title_short | The forkhead transcription factor FOXP2 is required for regulation of p21WAF1/CIP1 in 143B osteosarcoma cell growth arrest |
| title_sort | forkhead transcription factor foxp2 is required for regulation of p21waf1 cip1 in 143b osteosarcoma cell growth arrest |
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