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Article: Cell cycle-related kinase: A novel candidate oncogene in human glioblastoma

TitleCell cycle-related kinase: A novel candidate oncogene in human glioblastoma
Authors
Issue Date2007
PublisherOxford University Press. The Journal's web site is located at http://jncicancerspectrum.oxfordjournals.org/
Citation
Journal Of The National Cancer Institute, 2007, v. 99 n. 12, p. 936-948 How to Cite?
AbstractBackground: Median survival for patients with glioblastoma multiforme, the most aggressive glioma, is only 12-15 months, despite multimodal treatment that includes surgery, chemotherapy, and radiotherapy. Thus, identification of genes that control the progression of glioblastoma multiforme is crucial for devising new therapies. We investigated the involvement of cell cycle-related kinase (CCRK), a novel protein kinase that is homologous to cyclin-dependent kinase 7, in glioblastoma multiforme carcinogenesis. Methods: We analyzed the expression levels of CCRK in 26 glioma patient samples (19 high-grade and seven low-grade) and normal brain by semiquantitative reverse transcription-polymerase chain reaction assays. CCRK expression was knocked down in human glioma U-373 MG and U-87 MG cells with small-interfering RNAs and short hairpin RNAs (siCCRK and shCCRK, respectively), and cell proliferation, cell cycle distribution, and cyclin-dependent kinase 2 (CDK2) phosphorylation were examined. A subcutaneous nude mouse xenograft model (n = 4 mice per group) was used to study the effect of CCRK knockdown and overexpression on tumorigenicity and growth of glioblastoma multiforme cells in vivo. All statistical tests were two-sided. Results: CCRK mRNA was elevated at least 1.5-fold and as much as 3.7-fold in 14 (74%) of 19 high-grade glioblastoma multiforme patient samples and in four (80%) of five glioma cell lines examined compared with normal brain tissue. Suppression of CCRK by siCCRK inhibited the proliferation of U-373 MG and U-87 MG glioblastoma cells in a time- and dose-dependent manner. The growth-inhibiting effect of siCCRK was mediated via G 1- to S-phase cell cycle arrest and reduced CDK2 phosphorylation. CCRK knockdown statistically significantly suppressed glioma cell growth in vivo as indicated by the mean tumor volumes at week 6 after tumor cell injection (U-373-control = 1352 mm 3, U-373-shCCRK = 294 mm 3, difference = 1058 mm 3, 95% confidence interval [CI] = 677 to 1439 mm 3, P<.001; U-87-control = 1910 mm 3, U-87-shCCRK = 552 mm 3, difference = 1358 mm 3, 95% CI = 977 to 1739 mm 3, P<.001). Conclusions: CCRK is a candidate oncogene in glioblastoma multiforme tumorigenesis. © The Author 2007.
Persistent Identifierhttp://hdl.handle.net/10722/70093
ISSN
2015 Impact Factor: 11.37
2015 SCImago Journal Rankings: 6.192
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorNg, SSMen_HK
dc.contributor.authorCheung, YTen_HK
dc.contributor.authorAn, XMen_HK
dc.contributor.authorChen, YCen_HK
dc.contributor.authorLi, Men_HK
dc.contributor.authorHoiYee, Gen_HK
dc.contributor.authorCheung, Wen_HK
dc.contributor.authorSze, Jen_HK
dc.contributor.authorLai, Len_HK
dc.contributor.authorPeng, Yen_HK
dc.contributor.authorXia, HHXen_HK
dc.contributor.authorWong, BCYen_HK
dc.contributor.authorLeung, SYen_HK
dc.contributor.authorXie, Den_HK
dc.contributor.authorHe, MLen_HK
dc.contributor.authorKung, HFen_HK
dc.contributor.authorLin, MCen_HK
dc.date.accessioned2010-09-06T06:19:38Z-
dc.date.available2010-09-06T06:19:38Z-
dc.date.issued2007en_HK
dc.identifier.citationJournal Of The National Cancer Institute, 2007, v. 99 n. 12, p. 936-948en_HK
dc.identifier.issn0027-8874en_HK
dc.identifier.urihttp://hdl.handle.net/10722/70093-
dc.description.abstractBackground: Median survival for patients with glioblastoma multiforme, the most aggressive glioma, is only 12-15 months, despite multimodal treatment that includes surgery, chemotherapy, and radiotherapy. Thus, identification of genes that control the progression of glioblastoma multiforme is crucial for devising new therapies. We investigated the involvement of cell cycle-related kinase (CCRK), a novel protein kinase that is homologous to cyclin-dependent kinase 7, in glioblastoma multiforme carcinogenesis. Methods: We analyzed the expression levels of CCRK in 26 glioma patient samples (19 high-grade and seven low-grade) and normal brain by semiquantitative reverse transcription-polymerase chain reaction assays. CCRK expression was knocked down in human glioma U-373 MG and U-87 MG cells with small-interfering RNAs and short hairpin RNAs (siCCRK and shCCRK, respectively), and cell proliferation, cell cycle distribution, and cyclin-dependent kinase 2 (CDK2) phosphorylation were examined. A subcutaneous nude mouse xenograft model (n = 4 mice per group) was used to study the effect of CCRK knockdown and overexpression on tumorigenicity and growth of glioblastoma multiforme cells in vivo. All statistical tests were two-sided. Results: CCRK mRNA was elevated at least 1.5-fold and as much as 3.7-fold in 14 (74%) of 19 high-grade glioblastoma multiforme patient samples and in four (80%) of five glioma cell lines examined compared with normal brain tissue. Suppression of CCRK by siCCRK inhibited the proliferation of U-373 MG and U-87 MG glioblastoma cells in a time- and dose-dependent manner. The growth-inhibiting effect of siCCRK was mediated via G 1- to S-phase cell cycle arrest and reduced CDK2 phosphorylation. CCRK knockdown statistically significantly suppressed glioma cell growth in vivo as indicated by the mean tumor volumes at week 6 after tumor cell injection (U-373-control = 1352 mm 3, U-373-shCCRK = 294 mm 3, difference = 1058 mm 3, 95% confidence interval [CI] = 677 to 1439 mm 3, P<.001; U-87-control = 1910 mm 3, U-87-shCCRK = 552 mm 3, difference = 1358 mm 3, 95% CI = 977 to 1739 mm 3, P<.001). Conclusions: CCRK is a candidate oncogene in glioblastoma multiforme tumorigenesis. © The Author 2007.en_HK
dc.languageengen_HK
dc.publisherOxford University Press. The Journal's web site is located at http://jncicancerspectrum.oxfordjournals.org/en_HK
dc.relation.ispartofJournal of the National Cancer Instituteen_HK
dc.rightsJournal of the National Cancer Institute (Print). Copyright © Oxford University Press.en_HK
dc.titleCell cycle-related kinase: A novel candidate oncogene in human glioblastomaen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0027-8874&volume=99&issue=12&spage=936&epage=948&date=2007&atitle=Cell+Cycle-related+Kinase:+A+Novel+Candidate+Oncogene+in+Human+Glioblastomaen_HK
dc.identifier.emailNg, SSM: ssmng@hku.hken_HK
dc.identifier.emailWong, BCY: bcywong@hku.hken_HK
dc.identifier.emailLeung, SY: suetyi@hku.hken_HK
dc.identifier.emailLin, MC: mcllin@hkucc.hku.hken_HK
dc.identifier.authorityNg, SSM=rp00767en_HK
dc.identifier.authorityWong, BCY=rp00429en_HK
dc.identifier.authorityLeung, SY=rp00359en_HK
dc.identifier.authorityLin, MC=rp00746en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1093/jnci/djm011en_HK
dc.identifier.scopuseid_2-s2.0-34347257447en_HK
dc.identifier.hkuros131432en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-34347257447&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume99en_HK
dc.identifier.issue12en_HK
dc.identifier.spage936en_HK
dc.identifier.epage948en_HK
dc.identifier.isiWOS:000247918000009-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridNg, SSM=7403358718en_HK
dc.identifier.scopusauthoridCheung, YT=16678256500en_HK
dc.identifier.scopusauthoridAn, XM=12774780700en_HK
dc.identifier.scopusauthoridChen, YC=24075600300en_HK
dc.identifier.scopusauthoridLi, M=36067425800en_HK
dc.identifier.scopusauthoridHoiYee, G=17134833100en_HK
dc.identifier.scopusauthoridCheung, W=35080070600en_HK
dc.identifier.scopusauthoridSze, J=7003867625en_HK
dc.identifier.scopusauthoridLai, L=12445800200en_HK
dc.identifier.scopusauthoridPeng, Y=35249237100en_HK
dc.identifier.scopusauthoridXia, HHX=8757161400en_HK
dc.identifier.scopusauthoridWong, BCY=7402023340en_HK
dc.identifier.scopusauthoridLeung, SY=7202044886en_HK
dc.identifier.scopusauthoridXie, D=35070710200en_HK
dc.identifier.scopusauthoridHe, ML=35080389700en_HK
dc.identifier.scopusauthoridKung, HF=7402514190en_HK
dc.identifier.scopusauthoridLin, MC=7404816359en_HK

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