Key Laboratory of the Ministry of Education for Experimental Teratology, Department of Histology and Embryology, Shandong University School of Medicine, 44 Wenhua Xi Road, Jinan, Shandong, People's Republic of China.
J Pathol. 2011 Apr;223(5):672-82. doi: 10.1002/path.2827. Epub 2011 Feb 21.
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.
POU 家族转录因子 OCT4 对于维持胚胎干细胞的多能性和生成诱导多能干细胞是必需的。尽管 OCT4 显然在一些多能性生殖细胞瘤中表达，但它在人类体细胞肿瘤中的表达仍存在争议。一些研究表明，OCT4 在成体干细胞、体细胞癌中表达，进一步的研究表明在癌症干细胞中也有表达，而其他研究未能观察到这种情况。因此，确定 OCT4 是否在人类体细胞肿瘤中表达非常重要。通过使用 RT-PCR 和测序分析，我们在两种类型的人类实体瘤——神经胶质瘤和乳腺癌中发现了三个 OCT4 假基因（OCT4-pg1、OCT4-pg3 和 OCT4-pg4），但不包括 OCT4 基因，这些假基因已经从其中分离出了癌症干细胞。通过免疫化学和 Western blot 进一步证明了这些假基因的蛋白表达。与此同时，还表明 OCT4 假基因缺乏 OCT4 样活性。OCT4 剪接变体和各种假基因在人类体细胞肿瘤中的 mRNA 和蛋白水平上的表达可能会对 OCT4 在肿瘤发生中的表达和功能的研究结果的可靠性提出质疑。因此，在对癌症和干细胞中的 OCT4 表达进行研究时，需要采用不同的方法并结合适当的对照，以排除假阳性结果的可能性。
