北京大学医学部基础医学院病理学系张波教授领衔的研究小组在最新一期Oncogene上发表关于癌症发生的最新见解。
通常来说，人类癌症发生的两大细胞特征分别是：1.细胞中心体扩增；2.端粒缩短。这两大癌细胞的特征促使肿瘤发生过程中染色体不稳定。细胞中心体与端粒与DNA损伤修复机制有极大的关联，并且二者间也有一定的关联，有些调控端粒的因子同时还调控中心体，因此说中心体与端粒间有功能上的联系。
在本研究中，张波教授等研究人员发现，TEIF（telomerase transcriptional elements-interacting factor）是hTERT（human telomerase reverse transcriptase subunit）基因的反式作用子，TEIF分布在细胞循环过程中的中心体内，但是只在特定的调节下TEIF的转运量才会增加，其分别取决于其氨基端的结构。通过遗传技术人为地改造TEIF的表达量会影响中心体的功能，尤其对细胞有丝分裂会有影响。
研究发现TEIF的表达量会影响组织肉瘤中心体的扩增还与肿瘤组织学变化有关。TEIF参与DNA损伤应答，包括端粒酶功能失常和肿瘤发生，这表明TEIF在癌症发生过程中，影响中心体扩增与端粒功能。（生物谷Bioon.com）
生物谷推荐原始出处：
Oncogene 9 February 2009;doi: 10.1038/onc.2008.503
Localization of TEIF in the centrosome and its functional association with centrosome amplification in DNA damage, telomere dysfunction and human cancers
Y Gong1,2, Y Sun1,2, M A McNutt1, Q Sun1, L Hou1, H Liu1, Q Shen1, Y Ling1, Y Chi1 and B Zhang1
1Department of Pathology, Health Science Center of Peking University, Beijing, China
Correspondence: Dr B Zhang, Department of Pathology, Health Science Center of Peking University, 38 Xueyuan Road, Haidian District, Beijing 100191, China.
2These authors contributed equally to this work.
Abstract
Centrosome amplification and telomere shortening, which are commonly detected in human cancers, have been implicated in the induction of chromosome instability in tumorigenesis. The functions of these two structures are closely related to DNA damage repair machinery, and some factors that operate in the maintenance of telomeres also take part in the regulation of centrosome status, suggesting they are functionally linked. We report that TEIF (telomerase transcriptional elements-interacting factor), a transactivator of the hTERT (human telomerase reverse transcriptase subunit) gene, is distributed in the centrosome throughout the cell cycle, but its transport into the centrosome is increased under some conditions, and its distribution is dependent on its C-terminal domain. Experimental modulation of TEIF expression through overexpression, polypeptide expression or depletion affected centrosome status and increased abnormalities of cell mitosis. Localization of TEIF to the centrosome was also stimulated by treatment with genotoxic agents and experimental telomere dysfunction, accompanying centrosome amplification. Moreover, we demonstrated that the expression level of TEIF is not only closely correlated with centrosome amplification in soft tissue sarcomas but it is also significantly related to tumor histologic grade. Our data confirmed TEIF functions as a centrosome regulator. Its participation in DNA damage response, including telomere dysfunction and tumorigenesis, indicates TEIF is likely to be a factor involved in linking centrosome amplification and telomere dysfunction in cancer development.
