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Home > Mathematics and Science Textbooks > Chemistry > Functional Characterization of Cell-Cycle Related Kinase(ccrk) in Glioblastoma and Colon Cancer Carcinogenesis
Functional Characterization of Cell-Cycle Related Kinase(ccrk) in Glioblastoma and Colon Cancer Carcinogenesis

Functional Characterization of Cell-Cycle Related Kinase(ccrk) in Glioblastoma and Colon Cancer Carcinogenesis


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About the Book

This dissertation, "Functional Characterization of Cell-cycle Related Kinase(CCRK) in Glioblastoma and Colon Cancer Carcinogenesis" by Xiaomeng, An, 安曉萌, was obtained from The University of Hong Kong (Pokfulam, Hong Kong) and is being sold pursuant to Creative Commons: Attribution 3.0 Hong Kong License. The content of this dissertation has not been altered in any way. We have altered the formatting in order to facilitate the ease of printing and reading of the dissertation. All rights not granted by the above license are retained by the author. Abstract: Abstract of thesis entitled FUNCTIONAL CHARACTERIZATION OF CELL-CYCLE RELATED KINASE (CCRK) IN GLIOBLASTOMA AND COLON CANCER CARCINOGENESIS Submitted by An Xiaomeng for the degree of Doctor of Philosophy at The University of Hong Kong in August 2007 Cell-cycle related kinase (CCRK) is a newly identified 42 kDa protein which contains all 11 conserved sub domains characteristics of serine/threonine protein kinases, and is homologous to Cdks. In this study, the functions of CCRK in glioblastoma multiforme carcinogenesis and colon cancer carcinogenesis were investigated. CCRK expression levels were analyzed in 22 pairs of normal and colon cancer patient samples by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) and western blotting. It was found that the CCRK mRNA and protein expression levels were elevated in a majority of the colon cancer patient samples, and CCRK mRNA could be detected in all 7 colon cancer cell lines examined. Suppression of CCRK by small interfering RNA (siRNA) inhibited the proliferation of both glioblastoma cells and colon cancer cells. Consistently, stable clones of human colon cancer cells expressing short-hairpin RNA targeting CCRK (shCCRK) exhibited decreased cell proliferation rates. In vivo study showed that CCRK knock-down could significantly suppress glioma cell growth in nude mice as indicated by the mean tumor volumes by week 6 after tumor cell injection. Results from flow cytometry showed that the growth-inhibiting effect of siCCRK was mediated via G1 to S phase cell cycle arrest. CCRK has been reported to activate Cdk2 and was found to phosphorylate male germ cell-associated kinase (MAK)-related kinase at Thr-157 in mammalian cells. But whether CCRK could function as a second CDK-activating kinase (i.e., in addition to CDK7) was still unclear. It was found that transfection of siCCRK reduced the level of phosphorylated CDK2 and that CCRK coimmunoprecipitated with CDK2. These results suggest that CCRK is a CDK-activating kinase. Furthermore, CCRK was necessary for controlling the expression of Cdk2 binding partner, cyclin E, as well as the phsophorylation of the substrate of Cdk2-cyclin E complex, retinoblastoma protein (Rb). In addition, CCRK knock-down sensitized colon cancer cells to chemotherapeutic drugs such as 5-fluorouracil and camptothecin, suggesting that CCRK knock down may offer a feasible therapeutic strategy for colon cancer. In conclusion, this study has demonstrated that CCRK is involved in glioblastoma and colon cancer carcinogenesis, suggested that it is a potential therapeutic target for both glioblastoma and colon cancer. DOI: 10.5353/th_b3955821 Subjects: Protein kinases Cell cycle Colon (Anatomy) - Cancer Gliomas Carcinogenesis


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Product Details
  • ISBN-13: 9781361426821
  • Publisher: Open Dissertation Press
  • Publisher Imprint: Open Dissertation Press
  • Height: 279 mm
  • No of Pages: 162
  • Weight: 671 gr
  • ISBN-10: 1361426829
  • Publisher Date: 27 Jan 2017
  • Binding: Hardback
  • Language: English
  • Spine Width: 11 mm
  • Width: 216 mm


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Functional Characterization of Cell-Cycle Related Kinase(ccrk) in Glioblastoma and Colon Cancer Carcinogenesis
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