Expression of the Stem Cell Marker, Nanog, in Human Endometrial Adenocarcinoma
- 1 May 2011
- journal article
- pathology of-the-corpus
- Published by Ovid Technologies (Wolters Kluwer Health) in International Journal of Gynecological Pathology
- Vol. 33 (3), 262-270
- https://doi.org/10.1097/pgp.0b013e3182055a1f
Abstract
The embryonic stem cell self-renewal gene, Nanog, has been shown to be expressed in several tumor types and to regulate tumor development. The aim of this study was to carry out a detailed analysis of Nanog expression in human endometrial adenocarcinoma (EAC). Immunohistochemical analysis and reverse transcription-polymerase chain reaction were used to characterize Nanog, Sox2, and Oct4 expression in tissue arrays containing EAC, benign endometrium samples, and tumorosphere cells. Tumorosphere formation of EAC-derived cells in the stem cell culture medium was also analyzed. Nanog expression was then analyzed in secondary tumors initiated by the injection of tumorospheres or tumorosphere-derived differentiated cells into 15 female nude mice. Apoptosis and cell proliferation were detected in the fluorescence-activated cell sorter and 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide experiments, respectively. The Nanog protein was expressed in a majority of EAC samples (45 of 55, 81.8%), but not in benign endometrium samples (0 of 26, 0.0%). Oct4 and Sox2 were also commonly expressed in EAC samples (42 of 55, 76.4% and 39 of 55, 70.9%, respectively). Subsets of cancer cells from all EAC samples (15 of 15, 100%) exhibited the capacity to form Nanog-positive tumorospheres. The tumorospheres also expressed Nanog, Oct4, and Sox2 mRNA and showed a higher proliferation potential than differentiated cells. All 15 mice that were injected with tumorosphere cell-formed tumors, whereas only 3 of 15 mice injected with differentiated cells derived from tumorospheres developed tumors. All secondary xenograft tumors still expressed Nanog protein and Nanog, Oct4, and Sox2 mRNA, and had higher proliferation and lower apostosis than did differentiated cells. Overexpression of Nanog in EACs suggests that Nanog may represent a potential therapeutic target for EAC. In addition, Nanog may be useful as a biomarker in an immunohistochemical panel to differentiate between EAC and benign endometrial tissues. The expression of Nanog in tumorospheres may be indicative of the presence of a population of endometrial cancer stem cells, and its expression in xenograft tumors suggests that Nanog may also be associated with tumor metastasis.Keywords
This publication has 19 references indexed in Scilit:
- Regulation of the Nanog gene by both positive and negativecis-regulatory elements in embryonal carcinoma cells and embryonic stem cellsMolecular Reproduction and Development, 2008
- Embryonic Stem Cell Transcription Factor Signatures in the Diagnosis of Primary and Metastatic Germ Cell TumorsThe American Journal of Surgical Pathology, 2007
- Elevating the levels of Sox2 in embryonal carcinoma cells and embryonic stem cells inhibits the expression of Sox2:Oct-3/4 target genesNucleic Acids Research, 2007
- Reprogramming somatic cells into stem cellsReproduction, 2006
- Nanog transforms NIH3T3 cells and targets cell-type restricted genesBiochemical and Biophysical Research Communications, 2006
- Expression of Nanog gene promotes NIH3T3 cell proliferationBiochemical and Biophysical Research Communications, 2005
- Human embryonic stem cell genes OCT4, NANOG, STELLAR, and GDF3 are expressed in both seminoma and breast carcinomaCancer, 2005
- Stem and Progenitor-Like Cells Contribute to the Aggressive Behavior of Human Epithelial Ovarian CancerCancer Research, 2005
- Oct-3/4 and Sox2 Regulate Oct-3/4 Gene in Embryonic Stem CellsJournal of Biological Chemistry, 2005
- Regulatory Mechanisms in Stem Cell BiologyCell, 1997