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Article: Adenosine diphosphate-ribosylation factor 6 is required for epidermal growth factor-induced glioblastoma cell proliferation

TitleAdenosine diphosphate-ribosylation factor 6 is required for epidermal growth factor-induced glioblastoma cell proliferation
Authors
KeywordsAdenosine diphosphate-ribosylation factor 6
Epidermal growth factor
Glioma
Signaling pathway
SP1
Issue Date2009
PublisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www3.interscience.wiley.com/cgi-bin/jhome/28741
Citation
Cancer, 2009, v. 115 n. 21, p. 4959-4972 How to Cite?
AbstractBACKGROUND: Epidermal growth factor (EGF) signaling plays a pivotal role in gliomagenesis. The authors previously demonstrated that adenosine diphospate-ribosylation factor 6 (ARF6), a member of the Ras-related small guanosine-50-triphospate-binding protein family, is required for EFA6A-induced glioma cell migration and invasion. However, the role of ARF6 in EGF signaling is unknown. METHODS: The authors analyzed messenger RNA (mRNA) levels of ARF6 and EGF receptor (EGFR) in 16 high-grade glioma samples and in 6 low-grade glioma samples by reverse transcriptase-polymerase chain reaction analysis. To determine whether EGF induces ARF6 expression in human glioblastoma U87 cells through transcriptional regulation and EGFR activation, the levels of ARF6 were assayed in EGF-treated U87 cells that were preincubated with a transcriptional inhibitor (actinomycin D) and an EGFR tyrosine kinase inhibitor (PD153035), respectively. The downstream signaling of EGFR-mediated ARF6 up-regulation also was investigated using specific inhibitors of mitogen-activated protein kinase (MEK), phosphatidylinositol 30 kinase (PI3K), and Janus kinase 2. The involvement of SP1 in the downstream signaling was studied by using an SP1 inhibitor (mithramycin A). Small-interfering RNAs (siRNAs) targeting ARF6 were used to investigate the effects of ARF6 on EGF-mediated glioma cell proliferation. RESULTS: The results demonstrated that ARF6 and EGFR mRNA levels were elevated in glioma tissues. Furthermore, EGF stimulated ARF6 expression in U87 cells in a dose-dependent and time-dependant manner. This stimulation was caused by increased transcription of ARF6 and by activation of the MEK/extracellular signal-regulated kinase 1 and 2 (ERK1/2) and PI3K signaling pathways. It is noteworthy that SP1 was essential for EGF-induced ARF6 up-regulation. Finally, EGF-induced glioblastoma cell proliferation depended on ARF6, because the suppression of ARF6 by siRNA or by a dominant-negative mutant significantly inhibited EGF-induced cell proliferation. CONCLUSIONS: The results of the current study suggested that EGF-induced ARF6 expression plays a significant role in glioma cell proliferation. © 2009 American Cancer Society.
Persistent Identifierhttp://hdl.handle.net/10722/68948
ISSN
2015 Impact Factor: 5.649
2015 SCImago Journal Rankings: 3.188
ISI Accession Number ID
Funding AgencyGrant Number
Research Grants Council of the Hong KongCUHK467507
HKU7705/07M
Shing Institute of Health Sciences
Foundation of Guangzhou Science and Technology Bureau2005J1-C0311
Funding Information:

Supported by grants from the Research Grants Council of the Hong Kong Special Administrative Region, China (CUHK467507 to H.F.K. and HKU7705/07M to M.C.L.); donations for Li Ka Shing Institute of Health Sciences; and the Foundation of Guangzhou Science and Technology Bureau (2005J1-C0311 to H.F-K).

References

 

DC FieldValueLanguage
dc.contributor.authorLi, Men_HK
dc.contributor.authorWang, Jen_HK
dc.contributor.authorNg, SSMen_HK
dc.contributor.authorChan, CYen_HK
dc.contributor.authorHe, MLen_HK
dc.contributor.authorYu, Fen_HK
dc.contributor.authorLai, Len_HK
dc.contributor.authorShi, Cen_HK
dc.contributor.authorChen, Yen_HK
dc.contributor.authorYew, DTen_HK
dc.contributor.authorKung, HFen_HK
dc.contributor.authorLin, MCMen_HK
dc.date.accessioned2010-09-06T06:09:10Z-
dc.date.available2010-09-06T06:09:10Z-
dc.date.issued2009en_HK
dc.identifier.citationCancer, 2009, v. 115 n. 21, p. 4959-4972en_HK
dc.identifier.issn0008-543Xen_HK
dc.identifier.urihttp://hdl.handle.net/10722/68948-
dc.description.abstractBACKGROUND: Epidermal growth factor (EGF) signaling plays a pivotal role in gliomagenesis. The authors previously demonstrated that adenosine diphospate-ribosylation factor 6 (ARF6), a member of the Ras-related small guanosine-50-triphospate-binding protein family, is required for EFA6A-induced glioma cell migration and invasion. However, the role of ARF6 in EGF signaling is unknown. METHODS: The authors analyzed messenger RNA (mRNA) levels of ARF6 and EGF receptor (EGFR) in 16 high-grade glioma samples and in 6 low-grade glioma samples by reverse transcriptase-polymerase chain reaction analysis. To determine whether EGF induces ARF6 expression in human glioblastoma U87 cells through transcriptional regulation and EGFR activation, the levels of ARF6 were assayed in EGF-treated U87 cells that were preincubated with a transcriptional inhibitor (actinomycin D) and an EGFR tyrosine kinase inhibitor (PD153035), respectively. The downstream signaling of EGFR-mediated ARF6 up-regulation also was investigated using specific inhibitors of mitogen-activated protein kinase (MEK), phosphatidylinositol 30 kinase (PI3K), and Janus kinase 2. The involvement of SP1 in the downstream signaling was studied by using an SP1 inhibitor (mithramycin A). Small-interfering RNAs (siRNAs) targeting ARF6 were used to investigate the effects of ARF6 on EGF-mediated glioma cell proliferation. RESULTS: The results demonstrated that ARF6 and EGFR mRNA levels were elevated in glioma tissues. Furthermore, EGF stimulated ARF6 expression in U87 cells in a dose-dependent and time-dependant manner. This stimulation was caused by increased transcription of ARF6 and by activation of the MEK/extracellular signal-regulated kinase 1 and 2 (ERK1/2) and PI3K signaling pathways. It is noteworthy that SP1 was essential for EGF-induced ARF6 up-regulation. Finally, EGF-induced glioblastoma cell proliferation depended on ARF6, because the suppression of ARF6 by siRNA or by a dominant-negative mutant significantly inhibited EGF-induced cell proliferation. CONCLUSIONS: The results of the current study suggested that EGF-induced ARF6 expression plays a significant role in glioma cell proliferation. © 2009 American Cancer Society.en_HK
dc.languageengen_HK
dc.publisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www3.interscience.wiley.com/cgi-bin/jhome/28741en_HK
dc.relation.ispartofCanceren_HK
dc.rightsCancer. Copyright © John Wiley & Sons, Inc.en_HK
dc.subjectAdenosine diphosphate-ribosylation factor 6en_HK
dc.subjectEpidermal growth factoren_HK
dc.subjectGliomaen_HK
dc.subjectSignaling pathwayen_HK
dc.subjectSP1en_HK
dc.titleAdenosine diphosphate-ribosylation factor 6 is required for epidermal growth factor-induced glioblastoma cell proliferationen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0008-543X&volume=115&issue=21&spage=4959&epage=4972&date=2009&atitle=Adenosine+Diphosphate-ribosylation+Factor+6+is+Required+for+Epidermal+Growth+Factor-induced+Glioblastoma+Cell+Proliferationen_HK
dc.identifier.emailWang, J: jidewang@gmail.comen_HK
dc.identifier.emailNg, SSM: ssmng@hku.hken_HK
dc.identifier.emailLin, MCM: mcllin@hkucc.hku.hken_HK
dc.identifier.authorityWang, J=rp00491en_HK
dc.identifier.authorityNg, SSM=rp00767en_HK
dc.identifier.authorityLin, MCM=rp00746en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1002/cncr.24550en_HK
dc.identifier.pmid19642173-
dc.identifier.scopuseid_2-s2.0-70350501255en_HK
dc.identifier.hkuros161068en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-70350501255&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume115en_HK
dc.identifier.issue21en_HK
dc.identifier.spage4959en_HK
dc.identifier.epage4972en_HK
dc.identifier.isiWOS:000271167900012-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridLi, M=36067425800en_HK
dc.identifier.scopusauthoridWang, J=35309087500en_HK
dc.identifier.scopusauthoridNg, SSM=7403358718en_HK
dc.identifier.scopusauthoridChan, CY=22033276600en_HK
dc.identifier.scopusauthoridHe, ML=35080389700en_HK
dc.identifier.scopusauthoridYu, F=36986533000en_HK
dc.identifier.scopusauthoridLai, L=12445800200en_HK
dc.identifier.scopusauthoridShi, C=55175343900en_HK
dc.identifier.scopusauthoridChen, Y=24075600300en_HK
dc.identifier.scopusauthoridYew, DT=7007034694en_HK
dc.identifier.scopusauthoridKung, HF=7402514190en_HK
dc.identifier.scopusauthoridLin, MCM=7404816359en_HK

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