Correlation of dyskerin expression with active proliferation independent of telomerase.

Correlation of dyskerin expression with active proliferation independent of telomerase.
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DOI:
10.1002/hed.21579
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发表时间:
2011-07
影响因子:
2.9
通讯作者:
Patel, Reena
Patel, Reena
中科院分区:
医学2区
文献类型:
--
作者:
Alawi, Faizan;Lin, Ping;Ziober, Barry;Patel, Reena

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作为端粒酶复合物的重要组成部分,正常端粒酶活性所需的Dyskerin在肿瘤中经常过表达。Dyskerin在核糖体生物合成中也起重要作用。由于蛋白质合成在肿瘤发生过程中增加,这使我们假设dyskerin表达上调独立的细胞永生化机制。在口腔鳞状细胞癌(OSCC)和患者匹配的对照组中,以及在一组端粒酶阳性和端粒酶阴性细胞中,检测了Dyskerin和端粒酶逆转录酶(TERT)的表达。采用反义端粒酶抑制法检测端粒酶下调对dyskerin表达的影响。Dyskerin在口腔鳞状细胞癌和永生化和转化的角质形成细胞相对于原代细胞中经常过表达,独立于TERT和端粒酶活性。相反,dyskerin的表达与细胞增殖率密切相关。dyskerin在肿瘤发生中的作用与其在端粒酶复合物中的功能无关。
Dyskerin, which is an important component of the telomerase complex and is needed for normal telomerase activity, is frequently overexpressed in neoplasia. Dyskerin also plays an essential role in ribosome biogenesis. Since protein synthesis increases during tumorigenesis, this led us to hypothesize that dyskerin expression would be upregulated independently of the cell immortalization mechanism. Dyskerin and telomerase reverse transcriptase (TERT) expression were examined in oral squamous cell carcinomas (OSCC) and patient-matched controls, and in a panel of telomerase-positive and telomerase-negative cells. Antisense inhibition of TERT was used to test the effects of downregulation of telomerase on dyskerin expression. Dyskerin was frequently overexpressed in OSCC and in immortalized and transformed keratinocytes relative to primary cells, independently of TERT and telomerase activity. Instead, dyskerin expression strongly correlated with cell proliferation rates. The role of dyskerin in tumorigenesis does not correlate with its function within the telomerase complex.
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