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Article: Functional characterisation of cell cycle-related kinase (CCRK) in colorectal cancer carcinogenesis

TitleFunctional characterisation of cell cycle-related kinase (CCRK) in colorectal cancer carcinogenesis
Authors
KeywordsCarcinogenesis
CCRK
Cell cycle
Colorectal cancer
Issue Date2010
PublisherPergamon. The Journal's web site is located at http://www.elsevier.com/locate/ejca
Citation
European Journal Of Cancer, 2010, v. 46 n. 9, p. 1752-1761 How to Cite?
Abstract
Cell 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.
Persistent Identifierhttp://hdl.handle.net/10722/127422
ISSN
2013 Impact Factor: 4.819
2013 SCImago Journal Rankings: 2.806
ISI Accession Number ID
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.).

References

 

Author Affiliations
  1. The University of Hong Kong
  2. Sun Yat-Sen University
  3. Chinese University of Hong Kong
DC FieldValueLanguage
dc.contributor.authorAn, Xen_HK
dc.contributor.authorNg, SSen_HK
dc.contributor.authorXie, Den_HK
dc.contributor.authorZeng, YXen_HK
dc.contributor.authorSze, Jen_HK
dc.contributor.authorWang, Jen_HK
dc.contributor.authorChen, YCen_HK
dc.contributor.authorChow, BKCen_HK
dc.contributor.authorLu, Gen_HK
dc.contributor.authorPoon, WSen_HK
dc.contributor.authorKung, Hfen_HK
dc.contributor.authorWong, BCYen_HK
dc.contributor.authorLin, MCmen_HK
dc.date.accessioned2010-10-31T13:24:43Z-
dc.date.available2010-10-31T13:24:43Z-
dc.date.issued2010en_HK
dc.identifier.citationEuropean Journal Of Cancer, 2010, v. 46 n. 9, p. 1752-1761en_HK
dc.identifier.issn0959-8049en_HK
dc.identifier.urihttp://hdl.handle.net/10722/127422-
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.en_HK
dc.languageengen_HK
dc.publisherPergamon. The Journal's web site is located at http://www.elsevier.com/locate/ejcaen_HK
dc.relation.ispartofEuropean Journal of Canceren_HK
dc.subjectCarcinogenesisen_HK
dc.subjectCCRKen_HK
dc.subjectCell cycleen_HK
dc.subjectColorectal canceren_HK
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.titleFunctional characterisation of cell cycle-related kinase (CCRK) in colorectal cancer carcinogenesisen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0959-8049&volume=46&issue=9&spage=1752&epage=1761&date=2010&atitle=Functional+characterisation+of+cell+cycle-related+kinase+(CCRK)+in+colorectal+cancer+carcinogenesisen_HK
dc.identifier.emailNg, SS: ssmng@hku.hken_HK
dc.identifier.emailWang, J: jidewang@gmail.comen_HK
dc.identifier.emailChow, BKC: bkcc@hku.hken_HK
dc.identifier.emailWong, BCY: bcywong@hku.hken_HK
dc.identifier.emailLin, MCm: mcllin@hkucc.hku.hken_HK
dc.identifier.authorityNg, SS=rp00767en_HK
dc.identifier.authorityWang, J=rp00491en_HK
dc.identifier.authorityChow, BKC=rp00681en_HK
dc.identifier.authorityWong, BCY=rp00429en_HK
dc.identifier.authorityLin, MCm=rp00746en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.ejca.2010.04.007en_HK
dc.identifier.pmid20466538en_HK
dc.identifier.scopuseid_2-s2.0-77952581052en_HK
dc.identifier.hkuros176299en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-77952581052&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume46en_HK
dc.identifier.issue9en_HK
dc.identifier.spage1752en_HK
dc.identifier.epage1761en_HK
dc.identifier.isiWOS:000279387700038-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridAn, X=12774780700en_HK
dc.identifier.scopusauthoridNg, SS=7403358718en_HK
dc.identifier.scopusauthoridXie, D=35070710200en_HK
dc.identifier.scopusauthoridZeng, YX=7402981579en_HK
dc.identifier.scopusauthoridSze, J=7003867625en_HK
dc.identifier.scopusauthoridWang, J=35309087500en_HK
dc.identifier.scopusauthoridChen, YC=24075600300en_HK
dc.identifier.scopusauthoridChow, BKC=7102826193en_HK
dc.identifier.scopusauthoridLu, G=36619108300en_HK
dc.identifier.scopusauthoridPoon, WS=7103025507en_HK
dc.identifier.scopusauthoridKung, Hf=7402514190en_HK
dc.identifier.scopusauthoridWong, BCY=7402023340en_HK
dc.identifier.scopusauthoridLin, MCm=7404816359en_HK
dc.identifier.citeulike7176218-

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