Expression of OCT4 pseudogenes in human tumours: lessons from glioma and breast carcinoma

Expression of OCT4 pseudogenes in human tumours: lessons from glioma and breast carcinoma
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OCT4 假基因在人类肿瘤中的表达:神经胶质瘤和乳腺癌的教训

DOI:
10.1002/path.2827
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发表时间:
2011-04-01
影响因子:
7.3
通讯作者:
Hao, Aijun
Hao, Aijun
中科院分区:
医学1区
文献类型:
--
作者:
Zhao, Shidou;Yuan, Qiuhuan;Hao, Aijun

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POU家族转录因子OCT 4是维持胚胎干细胞的多能性和产生诱导多能干细胞所必需的。尽管OCT 4在一些多能生殖细胞肿瘤中表达,但其在人体肿瘤中的表达仍存在争议。一些研究表明,OCT 4在成体干细胞、体细胞癌和癌症干细胞中表达,而其他研究未能观察到这种情况。因此,确定OCT 4是否在人体肿瘤中表达是重要的。通过使用RT-PCR和测序分析,发现三个OCT 4假基因,即OCT 4-pg 1,OCT 4-pg 3和OCT 4-pg 4,但不包括OCT 4基因,在两种类型的人类实体瘤中表达,神经胶质瘤和乳腺癌,早期已从其中分离出癌症干细胞。免疫组化和免疫印迹法进一步证实了这些假基因的蛋白表达。沿着,显示OCT 4假基因缺乏OCT 4样活性。OCT 4剪接变体和各种假基因在mRNA和蛋白质水平上在人体肿瘤中的表达可能会对OCT 4在肿瘤发生中的表达和功能结果的可靠性提出质疑。因此,在癌症和干细胞中OCT 4表达的研究中,需要采用不同的方法和适当的对照来排除假阳性结果的可能性。版权所有© 2011大不列颠及爱尔兰病理学会。出版社:John Wiley & Sons,Ltd
The POU family transcription factor OCT4 is required for maintaining the pluripotency of embryonic stem cells and for generating induced pluripotent stem cells. Although OCT4 is clearly shown to be expressed in some pluripotent germ cell tumours, its expression in human somatic tumours remains controversial. Some studies have shown that OCT4 is expressed in adult stem cells, somatic cancers and, further, cancer stem cells, while other studies failed to make such an observation. It is thus important to ascertain whether OCT4 is expressed in human somatic tumours. By using RT‐PCR and sequencing analysis, three OCT4 pseudogenes, viz. OCT4‐pg1, OCT4‐pg3 and OCT4‐pg4 but excluding the OCT4 gene, were found to be expressed in two types of human solid tumours, glioma and breast carcinoma, from which cancer stem cells had earlier been isolated. The protein expression of these pseudogenes was further demonstrated by immunochemistry and western blotting. Along with this, it was shown that OCT4 pseudogenes lacked OCT4‐like activities. The expression of OCT4 splicing variant and various pseudogenes at both the mRNA and protein levels in human somatic tumours might call into question the reliability of the results regarding OCT4 expression and function in tumourigenesis. Hence, in investigations of OCT4 expression in cancers and stem cells, different approaches with appropriate controls would be desirable to exclude possibility of false‐positive results. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.