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Article: Antisense targeting protein kinase Cα and β1 inhibits gastric carcinogenesis

TitleAntisense targeting protein kinase Cα and β1 inhibits gastric carcinogenesis
Authors
Issue Date2004
PublisherAmerican Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/
Citation
Cancer Research, 2004, v. 64 n. 16, p. 5787-5794 How to Cite?
AbstractProtein kinase C (PKC) family, which functions through serine/threonine kinase activity, is involved in signal transduction pathways necessary for cell proliferation, differentiation, and apoptosis. Its critical role in neoplastic transformation and tumor invasion renders PKC a potential target for anticancer therapy. In this study, we investigated the effect of targeting individual PKCs on gastric carcinogenesis. We established gastric cancer cell lines stably expressing antisense PKCα, PKCβ 1, and PKCβ 2 cDNA. These stable transfectants were characterized by cell morphology, cell growth, apoptosis, and tumorigenicity in vitro and in vivo. PKCα-AS and PKCβ 1-AS transfectants showed a different morphology with flattened, long processes and decreased nuclear:cytoplasmic ratio compared with the control cells. Cell growth was markedly inhibited in PKCα-AS and PKCβ 1-AS transfectants. PKCα-AS and PKCβ 1-AS cells were more responsive to mitomycin C- or 5-fluorouracil-induced apoptosis. However, antisense targeting of PKCβ 2 did not have any significant effect on cell morphology, cell growth, or apoptosis. Furthermore, antisense inhibition of PKCα and PKCβ 1 markedly suppressed colony-forming efficiency in soft agar and in nude mice xenografts. Inhibition of PKCα or PKCβ 1 significantly suppressed transcriptional and DNA binding activity of activator protein in gastric cancer cells, suggesting that PKCα or PKCβ 1 exerts their effects on cell growth through regulation of activator protein activity. These data provide evidence that targeting PKCα and PKCβ 1 by antisense method is a promising therapy for gastric cancer.
Persistent Identifierhttp://hdl.handle.net/10722/168286
ISSN
2015 Impact Factor: 8.556
2015 SCImago Journal Rankings: 5.372
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorJiang, XHen_US
dc.contributor.authorTu, SPen_US
dc.contributor.authorCui, JTen_US
dc.contributor.authorLin, MCMen_US
dc.contributor.authorXia, HHXen_US
dc.contributor.authorWong, WMen_US
dc.contributor.authorChan, AOOen_US
dc.contributor.authorYuen, MFen_US
dc.contributor.authorJiang, SHen_US
dc.contributor.authorLam, SKen_US
dc.contributor.authorKung, HFen_US
dc.contributor.authorSoh, JWen_US
dc.contributor.authorWeinstein, IBen_US
dc.contributor.authorWong, BCYen_US
dc.date.accessioned2012-10-08T03:17:04Z-
dc.date.available2012-10-08T03:17:04Z-
dc.date.issued2004en_US
dc.identifier.citationCancer Research, 2004, v. 64 n. 16, p. 5787-5794en_US
dc.identifier.issn0008-5472en_US
dc.identifier.urihttp://hdl.handle.net/10722/168286-
dc.description.abstractProtein kinase C (PKC) family, which functions through serine/threonine kinase activity, is involved in signal transduction pathways necessary for cell proliferation, differentiation, and apoptosis. Its critical role in neoplastic transformation and tumor invasion renders PKC a potential target for anticancer therapy. In this study, we investigated the effect of targeting individual PKCs on gastric carcinogenesis. We established gastric cancer cell lines stably expressing antisense PKCα, PKCβ 1, and PKCβ 2 cDNA. These stable transfectants were characterized by cell morphology, cell growth, apoptosis, and tumorigenicity in vitro and in vivo. PKCα-AS and PKCβ 1-AS transfectants showed a different morphology with flattened, long processes and decreased nuclear:cytoplasmic ratio compared with the control cells. Cell growth was markedly inhibited in PKCα-AS and PKCβ 1-AS transfectants. PKCα-AS and PKCβ 1-AS cells were more responsive to mitomycin C- or 5-fluorouracil-induced apoptosis. However, antisense targeting of PKCβ 2 did not have any significant effect on cell morphology, cell growth, or apoptosis. Furthermore, antisense inhibition of PKCα and PKCβ 1 markedly suppressed colony-forming efficiency in soft agar and in nude mice xenografts. Inhibition of PKCα or PKCβ 1 significantly suppressed transcriptional and DNA binding activity of activator protein in gastric cancer cells, suggesting that PKCα or PKCβ 1 exerts their effects on cell growth through regulation of activator protein activity. These data provide evidence that targeting PKCα and PKCβ 1 by antisense method is a promising therapy for gastric cancer.en_US
dc.languageengen_US
dc.publisherAmerican Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/en_US
dc.relation.ispartofCancer Researchen_US
dc.subject.meshAnimalsen_US
dc.subject.meshApoptosis - Drug Effects - Geneticsen_US
dc.subject.meshCell Adhesion - Geneticsen_US
dc.subject.meshCell Division - Geneticsen_US
dc.subject.meshCell Line, Tumoren_US
dc.subject.meshDna, Antisense - Administration & Dosage - Geneticsen_US
dc.subject.meshFemaleen_US
dc.subject.meshHumansen_US
dc.subject.meshMiceen_US
dc.subject.meshMice, Inbred Balb Cen_US
dc.subject.meshMice, Nudeen_US
dc.subject.meshProtein Kinase C - Antagonists & Inhibitors - Geneticsen_US
dc.subject.meshProtein Kinase C-Alphaen_US
dc.subject.meshStomach Neoplasms - Enzymology - Genetics - Pathology - Therapyen_US
dc.subject.meshTranscription Factor Ap-1 - Antagonists & Inhibitorsen_US
dc.subject.meshTransfectionen_US
dc.subject.meshXenograft Model Antitumor Assaysen_US
dc.titleAntisense targeting protein kinase Cα and β1 inhibits gastric carcinogenesisen_US
dc.typeArticleen_US
dc.identifier.emailLin, MCM:mcllin@hkucc.hku.hken_US
dc.identifier.emailYuen, MF:mfyuen@hkucc.hku.hken_US
dc.identifier.emailWong, BCY:bcywong@hku.hken_US
dc.identifier.authorityLin, MCM=rp00746en_US
dc.identifier.authorityYuen, MF=rp00479en_US
dc.identifier.authorityWong, BCY=rp00429en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1158/0008-5472.CAN-03-1172en_US
dc.identifier.pmid15313921-
dc.identifier.scopuseid_2-s2.0-4143099402en_US
dc.identifier.hkuros91307-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-4143099402&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume64en_US
dc.identifier.issue16en_US
dc.identifier.spage5787en_US
dc.identifier.epage5794en_US
dc.identifier.isiWOS:000223321900037-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridJiang, XH=36089034900en_US
dc.identifier.scopusauthoridTu, SP=7202726555en_US
dc.identifier.scopusauthoridCui, JT=7401811557en_US
dc.identifier.scopusauthoridLin, MCM=7404816359en_US
dc.identifier.scopusauthoridXia, HHX=8757161400en_US
dc.identifier.scopusauthoridWong, WM=7403972413en_US
dc.identifier.scopusauthoridChan, AOO=7403167965en_US
dc.identifier.scopusauthoridYuen, MF=7102031955en_US
dc.identifier.scopusauthoridJiang, SH=7404453122en_US
dc.identifier.scopusauthoridLam, SK=7402279473en_US
dc.identifier.scopusauthoridKung, HF=7402514190en_US
dc.identifier.scopusauthoridSoh, JW=7006815014en_US
dc.identifier.scopusauthoridWeinstein, IB=36048534800en_US
dc.identifier.scopusauthoridWong, BCY=7402023340en_US

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