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Amphiregulin: Role in Mammary Gland Development and Breast Cancer

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

Abstract

Extensive epithelial cell proliferation underlies the ductal morphogenesis of puberty that generates the mammary tree that will eventually fill the fat pad. This estrogen-dependent process is believed to be essentially dependent on locally produced growth factors that act in a paracrine fashion. EGF-like growth factor ligands, acting through EGF receptors are some of the principal promoters of pubertal ductal morphogenesis. Amphiregulin is the most abundant EGF-like growth factor in the pubertal mammary gland. Its gene is transcriptionally regulated by ERα, and recent evidence identifies it as a key mediator of the estrogen-driven epithelial cell proliferation of puberty: The pubertal deficiency in mammary gland ductal morphogenesis in ERα, amphiregulin, and EGFR knockout mice phenocopy each other. As a prognostic indicator in human breast cancer, amphiregulin indicates an outcome identical to that predicted by ERα presence. Despite this, a range of studies both on preneoplastic human breast tissue and on cell culture based models of breast cancer, suggest a possibly significant role for amphiregulin in driving human breast cancer progression. Here we summarise our current understanding of amphiregulin’s contribution to mammary gland development and breast cancer progression.

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Abbreviations

Areg:

amphiregulin

ChIP:

chromatin immunoprecipitation

ECM:

extracellular matrix

EGF:

epidermal growth factor

EGFR:

epidermal growth factor receptor

ER:

estrogen receptor

ERE:

estrogen response element

FGF:

fibroblast growth factor

HELU:

hyperplastic enlarged lobular units

HGF:

hepatocyte growth factor

IGF:

insulin-like growth factor

KO:

knockout

Prlr:

prolactin receptor

PTHLH:

parathyroid hormone like hormone

TDLU:

terminal ductal lobular units

TEB:

terminal end bud

TGF:

transforming growth factor

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Acknowledgements

The studies carried out in our laboratory in University College Dublin were supported by grants from Science Foundation Ireland, the Health Research Board, Ireland and the EU Research Training Network programme.

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Authors and Affiliations

  1. School of Biomolecular and Biomedical Science, Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland

    Jean McBryan, Silvia Napoletano & Finian Martin

  2. Department of Laboratory Medicine, Cell and Experimental Pathology, Clinical Research Centre, Lund University, Malmo University Hospital, Entrance 72, House 91, Floor 11, 20502, Malmo, Sweden

    Jillian Howlin

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Correspondence to Finian Martin.

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McBryan, J., Howlin, J., Napoletano, S. et al. Amphiregulin: Role in Mammary Gland Development and Breast Cancer. J Mammary Gland Biol Neoplasia 13, 159–169 (2008). https://doi.org/10.1007/s10911-008-9075-7

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