Amphiregulin: Role in mammary gland development and breast cancer

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Amphiregulin: Role in mammary gland development and breast cancer. / McBryan, Jean; Howlin, Jillian; Napoletano, Silvia; Martin, Finian.

In: Journal of Mammary Gland Biology and Neoplasia, Vol. 13, No. 2, 2008, p. 159-169.

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McBryan, Jean ; Howlin, Jillian ; Napoletano, Silvia ; Martin, Finian. / Amphiregulin: Role in mammary gland development and breast cancer. In: Journal of Mammary Gland Biology and Neoplasia. 2008 ; Vol. 13, No. 2. pp. 159-169.

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TY - JOUR

T1 - Amphiregulin: Role in mammary gland development and breast cancer

AU - McBryan, Jean

AU - Howlin, Jillian

AU - Napoletano, Silvia

AU - Martin, Finian

PY - 2008

Y1 - 2008

N2 - 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 ER alpha, 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 ER alpha, 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 ER alpha 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.

AB - 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 ER alpha, 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 ER alpha, 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 ER alpha 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.

KW - puberty

KW - amphiregulin

KW - estrogen

KW - ductal morphogenesis

U2 - 10.1007/s10911-008-9075-7

DO - 10.1007/s10911-008-9075-7

M3 - Article

VL - 13

SP - 159

EP - 169

JO - Journal of Mammary Gland Biology and Neoplasia

JF - Journal of Mammary Gland Biology and Neoplasia

SN - 1083-3021

IS - 2

ER -