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Article: Functional characterisation of cell cycle-related kinase (CCRK) in colorectal cancer carcinogenesis
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TitleFunctional characterisation of cell cycle-related kinase (CCRK) in colorectal cancer carcinogenesis
 
AuthorsAn, X1
Ng, SS1
Xie, D2
Zeng, YX2
Sze, J1
Wang, J1
Chen, YC3
Chow, BKC1
Lu, G3
Poon, WS3
Kung, Hf2 3
Wong, BCY1
Lin, MCm3 1
 
KeywordsCarcinogenesis
CCRK
Cell cycle
Colorectal cancer
 
Issue Date2010
 
PublisherPergamon. The Journal's web site is located at http://www.elsevier.com/locate/ejca
 
CitationEuropean Journal Of Cancer, 2010, v. 46 n. 9, p. 1752-1761 [How to Cite?]
DOI: http://dx.doi.org/10.1016/j.ejca.2010.04.007
 
AbstractCell cycle-related kinase (CCRK) is a newly identified protein kinase homologous to Cdk7. We have previously shown that CCRK is a candidate oncogene in human glioblastoma. However, whether CCRK is a bona fide oncogene remains to be tested. The aim of this study was to investigate the role of CCRK in human colorectal cancer carcinogenesis. By Western blotting, we analysed the expression profile of CCRK protein in 10 colorectal cancer tissue samples and their adjacent normal colon tissues and in seven colorectal cancer cell lines. CCRK protein expression was also investigated by immunohistochemistry in a colorectal tissue microarray, which contained 120 cases of primary colorectal cancer and adjacent normal colorectal mucosa. The effects of CCRK knock-down on cell cycle profile and proliferation of colorectal cancer cells were examined by transfecting LoVo and DLD1 human colorectal cancer cell lines by either short-hairpin RNA (shCCRK) or small interfering RNA targeting CCRK (siCCRK). We found that CCRK protein levels were elevated by more than 1.5-fold in 70% of colorectal cancer patient samples examined and CCRK was detectable in all seven colorectal cancer cell lines tested. Colorectal tissue microarray indicated that overexpression of CCRK was detected in 62/109 (56.9%) of informative colorectal cancer cases and was significantly associated with the tumour pT and pN status (p < 0.05). Suppression of CCRK by siCCRK led to G1 phase cell cycle arrest and reduced cell growth. Consistently, stable clones of LoVo and DLD1 cells expressing shCCRK exhibited decreased cell proliferation rates. Furthermore, we showed that CCRK is required for the phosphorylation of Cdk2 (on Thr-160) and Rb (on Ser-795) and the expression of cyclin E. These results suggest for the first time that CCRK is involved in colorectal cancer carcinogenesis and G1/S cell cycle transition by regulating Cdk2, cyclin E and Rb. © 2010 Elsevier Ltd. All rights reserved.
 
ISSN0959-8049
2013 Impact Factor: 4.819
2013 SCImago Journal Rankings: 2.806
 
DOIhttp://dx.doi.org/10.1016/j.ejca.2010.04.007
 
ISI Accession Number IDWOS:000279387700038
Funding AgencyGrant Number
Research Grants Council of the Hong Kong Special Administrative Region, ChinaHKU/773809M
Nature Science Foundation of China30972884
Funding Information:

This work was supported by grants from the Research Grants Council of the Hong Kong Special Administrative Region, China (HKU/773809M to S.S.N.) and the Nature Science Foundation of China (No. 30972884 to D.X.).

 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorAn, X
 
dc.contributor.authorNg, SS
 
dc.contributor.authorXie, D
 
dc.contributor.authorZeng, YX
 
dc.contributor.authorSze, J
 
dc.contributor.authorWang, J
 
dc.contributor.authorChen, YC
 
dc.contributor.authorChow, BKC
 
dc.contributor.authorLu, G
 
dc.contributor.authorPoon, WS
 
dc.contributor.authorKung, Hf
 
dc.contributor.authorWong, BCY
 
dc.contributor.authorLin, MCm
 
dc.date.accessioned2010-10-31T13:24:43Z
 
dc.date.available2010-10-31T13:24:43Z
 
dc.date.issued2010
 
dc.description.abstractCell cycle-related kinase (CCRK) is a newly identified protein kinase homologous to Cdk7. We have previously shown that CCRK is a candidate oncogene in human glioblastoma. However, whether CCRK is a bona fide oncogene remains to be tested. The aim of this study was to investigate the role of CCRK in human colorectal cancer carcinogenesis. By Western blotting, we analysed the expression profile of CCRK protein in 10 colorectal cancer tissue samples and their adjacent normal colon tissues and in seven colorectal cancer cell lines. CCRK protein expression was also investigated by immunohistochemistry in a colorectal tissue microarray, which contained 120 cases of primary colorectal cancer and adjacent normal colorectal mucosa. The effects of CCRK knock-down on cell cycle profile and proliferation of colorectal cancer cells were examined by transfecting LoVo and DLD1 human colorectal cancer cell lines by either short-hairpin RNA (shCCRK) or small interfering RNA targeting CCRK (siCCRK). We found that CCRK protein levels were elevated by more than 1.5-fold in 70% of colorectal cancer patient samples examined and CCRK was detectable in all seven colorectal cancer cell lines tested. Colorectal tissue microarray indicated that overexpression of CCRK was detected in 62/109 (56.9%) of informative colorectal cancer cases and was significantly associated with the tumour pT and pN status (p < 0.05). Suppression of CCRK by siCCRK led to G1 phase cell cycle arrest and reduced cell growth. Consistently, stable clones of LoVo and DLD1 cells expressing shCCRK exhibited decreased cell proliferation rates. Furthermore, we showed that CCRK is required for the phosphorylation of Cdk2 (on Thr-160) and Rb (on Ser-795) and the expression of cyclin E. These results suggest for the first time that CCRK is involved in colorectal cancer carcinogenesis and G1/S cell cycle transition by regulating Cdk2, cyclin E and Rb. © 2010 Elsevier Ltd. All rights reserved.
 
dc.description.naturelink_to_subscribed_fulltext
 
dc.identifier.citationEuropean Journal Of Cancer, 2010, v. 46 n. 9, p. 1752-1761 [How to Cite?]
DOI: http://dx.doi.org/10.1016/j.ejca.2010.04.007
 
dc.identifier.citeulike7176218
 
dc.identifier.doihttp://dx.doi.org/10.1016/j.ejca.2010.04.007
 
dc.identifier.epage1761
 
dc.identifier.hkuros176299
 
dc.identifier.isiWOS:000279387700038
Funding AgencyGrant Number
Research Grants Council of the Hong Kong Special Administrative Region, ChinaHKU/773809M
Nature Science Foundation of China30972884
Funding Information:

This work was supported by grants from the Research Grants Council of the Hong Kong Special Administrative Region, China (HKU/773809M to S.S.N.) and the Nature Science Foundation of China (No. 30972884 to D.X.).

 
dc.identifier.issn0959-8049
2013 Impact Factor: 4.819
2013 SCImago Journal Rankings: 2.806
 
dc.identifier.issue9
 
dc.identifier.openurl
 
dc.identifier.pmid20466538
 
dc.identifier.scopuseid_2-s2.0-77952581052
 
dc.identifier.spage1752
 
dc.identifier.urihttp://hdl.handle.net/10722/127422
 
dc.identifier.volume46
 
dc.languageeng
 
dc.publisherPergamon. The Journal's web site is located at http://www.elsevier.com/locate/ejca
 
dc.publisher.placeUnited Kingdom
 
dc.relation.ispartofEuropean Journal of Cancer
 
dc.relation.referencesReferences in Scopus
 
dc.subject.meshBlotting, Western
 
dc.subject.meshCell Cycle - physiology
 
dc.subject.meshColorectal Neoplasms - etiology
 
dc.subject.meshCyclin-Dependent Kinases - physiology
 
dc.subject.meshNeoplasm Proteins - physiology
 
dc.subjectCarcinogenesis
 
dc.subjectCCRK
 
dc.subjectCell cycle
 
dc.subjectColorectal cancer
 
dc.titleFunctional characterisation of cell cycle-related kinase (CCRK) in colorectal cancer carcinogenesis
 
dc.typeArticle
 
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Author Affiliations
  1. The University of Hong Kong
  2. Sun Yat-Sen University
  3. Chinese University of Hong Kong