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Heterogeneity of telomerase reverse transcriptase mutation and expression, telomerase activity and telomere length across human cancer cell lines cultured in vitro
Experimental Cell Research ( IF 3.7 ) Pub Date : 2020-09-21 , DOI: 10.1016/j.yexcr.2020.112298
Marta Dratwa , Barbara Wysoczanska , Eliza Turlej , Artur Anisiewicz , Magdalena Maciejewska , Joanna Wietrzyk , Katarzyna Bogunia-Kubik

Promoter region of the telomerase reverse transcriptase gene (TERTp) constitutes a regulatory element capable to affect TERT expression (TE), telomerase activity (TA) and telomere length (TL). TERTp mutation status, TL, TA and TE were assessed in 27 in vitro cultured human cell lines, including 11 solid tumour, 13 haematological and 3 normal cell lines. C228T and C250T TERTp mutations were detected in 5 solid tumour and none of haematological cell lines (p = 0.0100). As compared to other solid tumour cell lines, those with the presence of somatic mutations were characterized by: shorter TL, lower TA and TE. Furthermore, cell lines carrying TERTp mutations showed a linear correlation between TE and TA (R = 0.9708, p = 0.0021). Moreover, haematological cell lines exhibited higher TE compared to solid tumour cell lines (p = 0.0007). TL and TA were correlated in both solid tumour (R = 0.4875, p = 0.0169) and haematological (R = 0.4719, p = 0.0095) cell lines. Our results based on the in vitro model suggest that oncogenic processes may differ between solid tumours and haematological malignancies with regard to their TERT gene regulation mechanisms.



中文翻译:

体外培养的人类癌细胞系中端粒酶逆转录酶突变与表达,端粒酶活性和端粒长度的异质性

端粒酶逆转录酶基因(TERTp)的启动子区域构成了能够影响TERT表达(TE),端粒酶活性(TA)和端粒长度(TL)的调节元件。在27种体外培养的人细胞系中评估了TERTp突变状态,TL,TA和TE ,包括11种实体瘤,13种血液学和3种正常细胞系。在5例实体瘤中,未检测到C228T和C250T TERTp突变,血液细胞系均未检测到(P  = 0.0100)。与其他实体瘤细胞系相比,那些存在体细胞突变的细胞系的特征是:TL较短,TA和TE较低。此外,携带TERTp的细胞系突变显示TE和TA之间线性相关(R = 0.9708,p = 0.0021)。此外,与实体瘤细胞系相比,血液细胞系表现出更高的TE(p  = 0.0007)。TL和TA在实体瘤(R = 0.4875,p  = 0.0169)和血液学(R = 0.4719,p  = 0.0095)细胞系中均相关。我们基于体外模型的结果表明,实体瘤和血液恶性肿瘤的致癌过程可能在TERT基因调控机制方面有所不同。

更新日期:2020-09-23
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