Expression of the pluripotency transcription factor OCT4 in the normal and aberrant mammary gland
Breast cancers with lactating features, some of which are associated with pregnancy and lactation, are often poorly differentiated, lack estrogen receptor, progesterone receptor and HER2 expression and have high mortality. Very little is known about the molecular mechanisms that drive uncontrolled c...
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doaj-772655c9aac4409e802deec644e7008d2020-11-24T22:28:09ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2013-04-01310.3389/fonc.2013.0007948555Expression of the pluripotency transcription factor OCT4 in the normal and aberrant mammary glandFoteini eHassiotou0Anna eHepworth1Adriana eBeltran2Michelle eMathews3Alison eStuebe4Peter eHartmann5Luis eFilgueira6Pilar eBlancafort7University of Western AustraliaUniversity of Western AustraliaUniversity of North CarolinaUniversity of North CarolinaUniversity of North CarolinaUniversity of Western AustraliaUniversity of FribourgUniversity of Western AustraliaBreast cancers with lactating features, some of which are associated with pregnancy and lactation, are often poorly differentiated, lack estrogen receptor, progesterone receptor and HER2 expression and have high mortality. Very little is known about the molecular mechanisms that drive uncontrolled cell proliferation in these tumors and confer lactating features. We have recently reported expression of OCT4 and associated embryonic stem cell (ESC) self-renewal genes in the normal lactating breast and breastmilk stem cells (hBSCs). This prompted us to examine OCT4 expression in breast cancers with lactating features and compare it with that observed during normal lactation, using rare specimens of human lactating breast. In accordance with previous literature, the normal resting breast (from non-pregnant, non-lactating women) showed minimal OCT4 nuclear expression (0.9%). However, this increased in the normal lactating breast (11.4%), with further increase in lactating adenomas, lactating carcinomas and pregnancy-associated breast cancer (30.7-48.3%). OCT4 was expressed in the epithelium and at lower levels in the stroma, and was co-localized with NANOG. Comparison of normal non-tumorigenic hBSCs with OCT4-overexpressing tumorigenic breast cell lines (OTBCs) demonstrated upregulation of OCT4, SOX2 and NANOG in both systems, but OTBCs expressed OCT4 at significantly higher levels than SOX2 and NANOG. Similar to hBSCs, OTBCs displayed multi-lineage differentiation potential, including the ability to differentiate into functional lactocytes synthesizing milk proteins both in vitro and in vivo. Based on these findings, we propose a hypothesis of normal and malignant transformation in the breast, which centers on OCT4 and its associated gene network. Although minimal expression of these embryonic genes can be seen in the breast in its resting state throughout life, a controlled program of upregulation of this gene network may be a potential regulator of the normal remodelihttp://journal.frontiersin.org/Journal/10.3389/fonc.2013.00079/fullTranscription Factorsbreast cancerCancer stem cellproliferationmammary glandself-renewal |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Foteini eHassiotou Anna eHepworth Adriana eBeltran Michelle eMathews Alison eStuebe Peter eHartmann Luis eFilgueira Pilar eBlancafort |
spellingShingle |
Foteini eHassiotou Anna eHepworth Adriana eBeltran Michelle eMathews Alison eStuebe Peter eHartmann Luis eFilgueira Pilar eBlancafort Expression of the pluripotency transcription factor OCT4 in the normal and aberrant mammary gland Frontiers in Oncology Transcription Factors breast cancer Cancer stem cell proliferation mammary gland self-renewal |
author_facet |
Foteini eHassiotou Anna eHepworth Adriana eBeltran Michelle eMathews Alison eStuebe Peter eHartmann Luis eFilgueira Pilar eBlancafort |
author_sort |
Foteini eHassiotou |
title |
Expression of the pluripotency transcription factor OCT4 in the normal and aberrant mammary gland |
title_short |
Expression of the pluripotency transcription factor OCT4 in the normal and aberrant mammary gland |
title_full |
Expression of the pluripotency transcription factor OCT4 in the normal and aberrant mammary gland |
title_fullStr |
Expression of the pluripotency transcription factor OCT4 in the normal and aberrant mammary gland |
title_full_unstemmed |
Expression of the pluripotency transcription factor OCT4 in the normal and aberrant mammary gland |
title_sort |
expression of the pluripotency transcription factor oct4 in the normal and aberrant mammary gland |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Oncology |
issn |
2234-943X |
publishDate |
2013-04-01 |
description |
Breast cancers with lactating features, some of which are associated with pregnancy and lactation, are often poorly differentiated, lack estrogen receptor, progesterone receptor and HER2 expression and have high mortality. Very little is known about the molecular mechanisms that drive uncontrolled cell proliferation in these tumors and confer lactating features. We have recently reported expression of OCT4 and associated embryonic stem cell (ESC) self-renewal genes in the normal lactating breast and breastmilk stem cells (hBSCs). This prompted us to examine OCT4 expression in breast cancers with lactating features and compare it with that observed during normal lactation, using rare specimens of human lactating breast. In accordance with previous literature, the normal resting breast (from non-pregnant, non-lactating women) showed minimal OCT4 nuclear expression (0.9%). However, this increased in the normal lactating breast (11.4%), with further increase in lactating adenomas, lactating carcinomas and pregnancy-associated breast cancer (30.7-48.3%). OCT4 was expressed in the epithelium and at lower levels in the stroma, and was co-localized with NANOG. Comparison of normal non-tumorigenic hBSCs with OCT4-overexpressing tumorigenic breast cell lines (OTBCs) demonstrated upregulation of OCT4, SOX2 and NANOG in both systems, but OTBCs expressed OCT4 at significantly higher levels than SOX2 and NANOG. Similar to hBSCs, OTBCs displayed multi-lineage differentiation potential, including the ability to differentiate into functional lactocytes synthesizing milk proteins both in vitro and in vivo. Based on these findings, we propose a hypothesis of normal and malignant transformation in the breast, which centers on OCT4 and its associated gene network. Although minimal expression of these embryonic genes can be seen in the breast in its resting state throughout life, a controlled program of upregulation of this gene network may be a potential regulator of the normal remodeli |
topic |
Transcription Factors breast cancer Cancer stem cell proliferation mammary gland self-renewal |
url |
http://journal.frontiersin.org/Journal/10.3389/fonc.2013.00079/full |
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