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

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. (C) 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.