The Relationship Between Telomerase Activity and Cell-Cycle Regulators, Cyclin D1, Cdk2 and Cdk4, in Human Hepatocellular Carcinomas

碩士 === 國防醫學院 === 病理及寄生蟲學研究所 === 86 ===   Deregulation of the cell cycle by abnormal expression of some cell cycle regulatory proteins is a common finding in malignant tumors and might be a prerequisite for cancer development. During G1 phase, cyclin D1 with its associated protein, cyclin dependent k...

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Bibliographic Details
Main Author: 邱紹智
Other Authors: 韓鴻志
Format: Others
Language:zh-TW
Published: 1998
Online Access:http://ndltd.ncl.edu.tw/handle/04941232291589320022
Description
Summary:碩士 === 國防醫學院 === 病理及寄生蟲學研究所 === 86 ===   Deregulation of the cell cycle by abnormal expression of some cell cycle regulatory proteins is a common finding in malignant tumors and might be a prerequisite for cancer development. During G1 phase, cyclin D1 with its associated protein, cyclin dependent kinase (cdk)4, induces inactivation of retinoblastoma protein (pRB) by phosphorylation and S phase progression. Telomerase, a ribonucleoprotein, compensates for the continued shortening telomere length by adding hexameric (TTAGGG)repeat to the telomeric ends of the chromosomes. Telomerase activity is expressed in almost all malignant tumors, but is rately detected in normal somatic cells. In the tissues of 25 hepatocellular carcinoma (HCC), we analyzed the telomerase activity level and focused on abnormal expression of G1phase regulators, cyclin D1, cdk4 and cdk2. The fraction of telomerase positive tumors was 84% (21/25) and only five non-tumorous tissue had very weak telomerase activity. In most of HCC, the expression of cyclin D1, cdk4 and cdk2 was lower than in non-tumorous tissue and had large range of expression in tumors. We also found the difference of cyclin D1, cdk4 and cdk2 between tumor and non-tumorous tissues was very obvious. Between the variation of tumor and non-tumorous tissues, the change of the telomerase activity was related to the difference of cyclin D1, cdk4 and cdk2, and was presented a descending trend. Our results re-confirmed that the telomerase activity was an apparent tumor marker helpful for dtagnosis of HCC, The high change of telomerase activity between tumor and non - tumorous tissue is associated with a lower expression of cyclin D1, cdk4 and cdk2. It indicated that these cell cycle regulators did not exhibit a strict role in HCC cell proliferation and mmortalization. We suggested that there were other unidentified factors which controlled the progressive cell cycle of tumor and might be correlated with the telomerase activity.