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Differential Expression of Oct4 Variants and Pseudogenes in Normal Urothelium and Urothelial Cancer
- Source :
- The American Journal of Pathology. 183:1128-1136
- Publication Year :
- 2013
- Publisher :
- Elsevier BV, 2013.
-
Abstract
- The transcription factor octamer-binding protein 4 (Oct4; encoded by POU5F1) has a key role in maintaining embryonic stem cell pluripotency during early embryonic development and it is required for generation of induced pluripotent stem cells. Controversy exists concerning Oct4 expression in somatic tissues, with reports that Oct4 is expressed in normal and in neoplastic urothelium carrying implications for a bladder cancer stem cell phenotype. Here, we show that the pluripotency-associated Oct4A transcript was absent from cultures of highly regenerative normal human urothelial cells and from low-grade to high-grade urothelial carcinoma cell lines, whereas alternatively spliced variants and transcribed pseudogenes were expressed in abundance. Immunolabeling and immunoblotting studies confirmed the absence of Oct4A in normal and neoplastic urothelial cells and tissues, but indicated the presence of alternative isoforms or potentially translated pseudogenes. The stable forced expression of Oct4A in normal human urothelial cells in vitro profoundly inhibited growth and affected morphology, but protein expression was rapidly down-regulated. Our findings demonstrate that pluripotency-associated isoform Oct4A is not expressed by normal or malignant human urothelium and therefore is unlikely to play a role in a cancer stem cell phenotype. However, our findings also indicate that urothelium expresses a variety of other Oct4 splice-variant isoforms and transcribed pseudogenes that warrant further study.
- Subjects :
- Pathology
medicine.medical_specialty
Transcription, Genetic
Somatic cell
Gene Expression Profiling
SOXB1 Transcription Factors
Pseudogene
Immunoblotting
Biology
Phenotype
Embryonic stem cell
Pathology and Forensic Medicine
Cell biology
Gene Expression Regulation, Neoplastic
Urinary Bladder Neoplasms
Cell culture
Cancer stem cell
Cell Line, Tumor
medicine
Humans
Urothelium
Induced pluripotent stem cell
Octamer Transcription Factor-3
Pseudogenes
Subjects
Details
- ISSN :
- 00029440
- Volume :
- 183
- Database :
- OpenAIRE
- Journal :
- The American Journal of Pathology
- Accession number :
- edsair.doi.dedup.....ca83ad7f1c1fc7b8b818d9961c686ac2