Autochthonous Mouse Melanoma and Mammary Tumors do not Express the Pluripotency Genes Oct4 and Nanog

The homeodomain transcription factors Oct4 and Nanog maintain pluripotency and self-renewal in embryonic stem cells. In somatic cells, inappropriate expression of these genes has been associated with loss of differentiation, malignant transformation, and the acquisition of cancer stem cell-like prop...

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Main Authors:	Schreiber, Caroline, Kuch, Vanessa, Umansky, Viktor, Sleeman, Jonathan P.
Format:	Online
Language:	English
Published:	Public Library of Science 2013
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3585372/

id	pubmed-3585372
recordtype	oai_dc
spelling	pubmed-35853722013-03-06 Autochthonous Mouse Melanoma and Mammary Tumors do not Express the Pluripotency Genes Oct4 and Nanog Schreiber, Caroline Kuch, Vanessa Umansky, Viktor Sleeman, Jonathan P. Research Article The homeodomain transcription factors Oct4 and Nanog maintain pluripotency and self-renewal in embryonic stem cells. In somatic cells, inappropriate expression of these genes has been associated with loss of differentiation, malignant transformation, and the acquisition of cancer stem cell-like properties. As cancer stem cells have been suggested to underlie the growth and malignancy of tumors, Oct4 and Nanog may represent therapeutic targets. Their expression could also act as a marker of the cancer stem cell population, permitting its isolation and characterisation. Nevertheless, the existence of multiple pseudogenes and isoforms of these genes has complicated the interpretation of the data that supports a role for Oct4 and Nanog in the cancer context. Here we addressed this issue using knockin mice in which IRES elements are used to allow GFP expression under the control of the endogenous Oct4 or Nanog promoters, while maintaining correct expression of the Oct4 or Nanog gene. These mice were crossed with MT/ret mice that develop melanomas, and with MMTV-PyMT mice and MMTV-Neu mice that develop mammary adenocarcinomas. We analysed the tumors that developed in these compound mice for GFP expression. In this way we could assess transcription of Oct4 and Nanog in autochthonous cancers without the complication of factors such as pseudogene expression, alternative splicing and antibody specificity. Both the Oct4 and Nanog knockin tumor-bearing mice expressed GFP in blastocysts and testes as expected. However, we could find no evidence for expression of the GFP reporter above background levels in tumors using FACS, qPCR and immunohistochemistry. Furthermore, cultivation of Oct4GFP and NanogGFP MMTV-PyMT tumor cells either adherently or as spheroids had no effect on the expression of the GFP reporter. Together these data suggest that Oct4 and Nanog are not expressed in tumor cells that arise in the autochthonous cancer models studied here. Public Library of Science 2013-02-28 /pmc/articles/PMC3585372/ /pubmed/23468991 http://dx.doi.org/10.1371/journal.pone.0057465 Text en © 2013 Schreiber et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Schreiber, Caroline Kuch, Vanessa Umansky, Viktor Sleeman, Jonathan P.
spellingShingle	Schreiber, Caroline Kuch, Vanessa Umansky, Viktor Sleeman, Jonathan P. Autochthonous Mouse Melanoma and Mammary Tumors do not Express the Pluripotency Genes Oct4 and Nanog
author_facet	Schreiber, Caroline Kuch, Vanessa Umansky, Viktor Sleeman, Jonathan P.
author_sort	Schreiber, Caroline
title	Autochthonous Mouse Melanoma and Mammary Tumors do not Express the Pluripotency Genes Oct4 and Nanog
title_short	Autochthonous Mouse Melanoma and Mammary Tumors do not Express the Pluripotency Genes Oct4 and Nanog
title_full	Autochthonous Mouse Melanoma and Mammary Tumors do not Express the Pluripotency Genes Oct4 and Nanog
title_fullStr	Autochthonous Mouse Melanoma and Mammary Tumors do not Express the Pluripotency Genes Oct4 and Nanog
title_full_unstemmed	Autochthonous Mouse Melanoma and Mammary Tumors do not Express the Pluripotency Genes Oct4 and Nanog
title_sort	autochthonous mouse melanoma and mammary tumors do not express the pluripotency genes oct4 and nanog
description	The homeodomain transcription factors Oct4 and Nanog maintain pluripotency and self-renewal in embryonic stem cells. In somatic cells, inappropriate expression of these genes has been associated with loss of differentiation, malignant transformation, and the acquisition of cancer stem cell-like properties. As cancer stem cells have been suggested to underlie the growth and malignancy of tumors, Oct4 and Nanog may represent therapeutic targets. Their expression could also act as a marker of the cancer stem cell population, permitting its isolation and characterisation. Nevertheless, the existence of multiple pseudogenes and isoforms of these genes has complicated the interpretation of the data that supports a role for Oct4 and Nanog in the cancer context. Here we addressed this issue using knockin mice in which IRES elements are used to allow GFP expression under the control of the endogenous Oct4 or Nanog promoters, while maintaining correct expression of the Oct4 or Nanog gene. These mice were crossed with MT/ret mice that develop melanomas, and with MMTV-PyMT mice and MMTV-Neu mice that develop mammary adenocarcinomas. We analysed the tumors that developed in these compound mice for GFP expression. In this way we could assess transcription of Oct4 and Nanog in autochthonous cancers without the complication of factors such as pseudogene expression, alternative splicing and antibody specificity. Both the Oct4 and Nanog knockin tumor-bearing mice expressed GFP in blastocysts and testes as expected. However, we could find no evidence for expression of the GFP reporter above background levels in tumors using FACS, qPCR and immunohistochemistry. Furthermore, cultivation of Oct4GFP and NanogGFP MMTV-PyMT tumor cells either adherently or as spheroids had no effect on the expression of the GFP reporter. Together these data suggest that Oct4 and Nanog are not expressed in tumor cells that arise in the autochthonous cancer models studied here.
publisher	Public Library of Science
publishDate	2013
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3585372/
_version_	1611958590352916480

Autochthonous Mouse Melanoma and Mammary Tumors do not Express the Pluripotency Genes Oct4 and Nanog

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