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Pregnancy and Stem Cell Behavior

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Journal of Mammary Gland Biology and Neoplasia Aims and scope Submit manuscript

Abstract

The identification of cancer-initiating epithelial subtypes (i.e. cancer stem cells) is important for gaining a more comprehensive understanding of the process of neoplastic transformation and tumorigenesis. Since reproductive history has a major impact on breast tumorigenesis, it is reasonable to assume that pregnancy and lactation have enduring effects on the cancer susceptibility of multipotent progenitors. Using the Cre-lox technology as a tool to genetically label pregnancy-hormone-responsive cells, we identified a mammary epithelial subtype that is abundant in parous females. These pregnancy-induced mammary epithelial cells (PI-MECs) originate from differentiating cells during the first pregnancy and lactation cycle. They do not undergo apoptosis during postlactational remodeling, and they persist throughout the remainder of a female’s life. In this review, we discuss the biological relevance of PI-MECs in multiparous females and their important stem cell-like features, such as self renewal, as well as their ability to produce progeny with diverse cellular fates. Using appropriate animal models, we further demonstrate that PI-MECs are cellular targets for pregnancy-enhanced mammary tumorigenesis.

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Abbreviations

BRCA1/2:

breast and ovarian cancer gene 1/2, early onset

Cre:

site-specific recombinase in bacteriophage P1 (catalyses recombination between loxP sites)

DMBA:

7,12-dimethylbenz[a] anthracene

ER:

estrogen receptor

IGF-1:

insulin-like growth factor 1

Jak2:

Janus kinase 2

LacZ:

gene encoding ß-galactosidase from E. coli

loxP:

locus of crossing (X-ing) over

LTR:

long terminal repeat

MMTV:

mouse mammary tumor virus

NCI:

National Cancer Institute

Neu:

a.k.a. Her2 or ErbB2, member of the epidermal growth factor receptor family

Nkcc1:

sodium, potassium, and chloride (Na+/K+/2Cl) transporter

NMU:

N-nitrosomethyl urea

PI-MECs:

parityinduced mammary epithelial cells

PyVMT:

polyoma middle T oncogene

Rosa:

transcriptionally active locus identified by gene trap in murine embryonic stem cells using a retroviral vector with Reverse-Orientation-Splice-Acceptor

Sca-1:

stem cell antigen 1 or lymphocyte activation protein 6A

Stat5:

signal transducer and activator of transcription 5

TEB:

terminal end bud

TGF-β1:

transforming growth factor beta 1

WAP:

whey acidic protein

Wnt1:

wingless-related MMTV integration site 1

X-Gal:

5-Bromo-4-chloro-3-indolyl-beta-D-galactopyranoside

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Authors and Affiliations

  1. Eppley Institute for Research in Cancer and Allied Diseases and the Department of Pathology and Microbiology, University of Nebraska Medical Center, Nebraska Medical Center, Omaha, Nebraska

    Kay-Uwe Wagner

  2. Mammary Biology and Tumorigenesis Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland

    Gilbert H. Smith

  3. Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, 986805 Nebraska Medical Center, Rm. 8009, Omaha, Nebraska, 68198-6805

    Kay-Uwe Wagner

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  1. Kay-Uwe Wagner
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Correspondence to Kay-Uwe Wagner.

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Wagner, KU., Smith, G.H. Pregnancy and Stem Cell Behavior. J Mammary Gland Biol Neoplasia 10, 25–36 (2005). https://doi.org/10.1007/s10911-005-2538-1

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