北京大學(xué)醫(yī)學(xué)部基礎(chǔ)醫(yī)學(xué)院病理學(xué)系張波教授領(lǐng)銜的研究小組在最新一期Oncogene上發(fā)表關(guān)于癌癥發(fā)生的最新見(jiàn)解,。
通常來(lái)說(shuō),，人類癌癥發(fā)生的兩大細(xì)胞特征分別是：1.細(xì)胞中心體擴(kuò)增；2.端?？s短,。這兩大癌細(xì)胞的特征促使腫瘤發(fā)生過(guò)程中染色體不穩(wěn)定,。細(xì)胞中心體與端粒與DNA損傷修復(fù)機(jī)制有極大的關(guān)聯(lián)，并且二者間也有一定的關(guān)聯(lián),，有些調(diào)控端粒的因子同時(shí)還調(diào)控中心體,，因此說(shuō)中心體與端粒間有功能上的聯(lián)系。
在本研究中,，張波教授等研究人員發(fā)現(xiàn),，TEIF（telomerase transcriptional elements-interacting factor）是hTERT（human telomerase reverse transcriptase subunit）基因的反式作用子，TEIF分布在細(xì)胞循環(huán)過(guò)程中的中心體內(nèi),，但是只在特定的調(diào)節(jié)下TEIF的轉(zhuǎn)運(yùn)量才會(huì)增加,，其分別取決于其氨基端的結(jié)構(gòu)。通過(guò)遺傳技術(shù)人為地改造TEIF的表達(dá)量會(huì)影響中心體的功能,，尤其對(duì)細(xì)胞有絲分裂會(huì)有影響,。
研究發(fā)現(xiàn)TEIF的表達(dá)量會(huì)影響組織肉瘤中心體的擴(kuò)增還與腫瘤組織學(xué)變化有關(guān)。TEIF參與DNA損傷應(yīng)答,，包括端粒酶功能失常和腫瘤發(fā)生,，這表明TEIF在癌癥發(fā)生過(guò)程中，影響中心體擴(kuò)增與端粒功能,。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
