Elevated Circulating IGF-I Promotes Mammary Gland Development and Proliferation

Dara Cannata, Danielle Lann, Yingjie Wu, Sebastien Elis, Hui Sun, Shoshana Yakar, Deborah A. Lazzarino, Teresa L. Wood, Derek LeRoith

Research output: Contribution to journalArticle

Abstract

Animal studies have shown that IGF-I is essential for mammary gland development. Previous studies have suggested that local IGF-I rather than circulating IGF-I is the major mediator of mammary gland development. In the present study we used the hepatic IGF-I transgenic (HIT) and IGF-I knockout/HIT (KO-HIT) mouse models to examine the effects of enhanced circulating IGF-I on mammary development in the presence and absence of local IGF-I. HIT mice express the rat IGF-I transgene under the transthyretin promoter in the liver and have elevated circulating IGF-I and normal tissue IGF-I levels. The KO-HIT mice have no tissue IGF-I and increased circulating IGF-I. Analysis of mammary gland development reveals a greater degree of complexity in HIT mice as compared to control and KO-HIT mice, which demonstrate similar degrees of mammary gland complexity. Immunohistochemical evaluation of glands of HIT mice also suggests an enhanced degree of proliferation of the mammary gland, whereas KO-HIT mice exhibit mammary gland proliferation similar to control mice. In addition, HIT mice have a higher percentage of proliferating myoepithelial and luminal cells than control mice, whereas KO-HIT mice have an equivalent percentage of proliferating myoepithelial and luminal cells as control mice. Thus, our findings show that elevated circulating IGF-I levels are sufficient to promote normal pubertal mammary epithelial development. However, HIT mice demonstrate more pronounced mammary gland development when compared to control and KO-HIT mice. This suggests that both local and endocrine IGF-I play roles in mammary gland development and that elevated circulating IGF-I accelerates mammary epithelial proliferation.

Original languageEnglish (US)
Pages (from-to)5751-5761
Number of pages11
JournalEndocrinology
Volume151
Issue number12
DOIs
StatePublished - Dec 2010

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Human Mammary Glands
Insulin-Like Growth Factor I
Transgenic Mice
Knockout Mice
Liver
Breast
Prealbumin

ASJC Scopus subject areas

  • Endocrinology

Cite this

Cannata, D., Lann, D., Wu, Y., Elis, S., Sun, H., Yakar, S., ... LeRoith, D. (2010). Elevated Circulating IGF-I Promotes Mammary Gland Development and Proliferation. Endocrinology, 151(12), 5751-5761. https://doi.org/10.1210/en.2010-0792

Elevated Circulating IGF-I Promotes Mammary Gland Development and Proliferation. / Cannata, Dara; Lann, Danielle; Wu, Yingjie; Elis, Sebastien; Sun, Hui; Yakar, Shoshana; Lazzarino, Deborah A.; Wood, Teresa L.; LeRoith, Derek.

In: Endocrinology, Vol. 151, No. 12, 12.2010, p. 5751-5761.

Research output: Contribution to journalArticle

Cannata, D, Lann, D, Wu, Y, Elis, S, Sun, H, Yakar, S, Lazzarino, DA, Wood, TL & LeRoith, D 2010, 'Elevated Circulating IGF-I Promotes Mammary Gland Development and Proliferation', Endocrinology, vol. 151, no. 12, pp. 5751-5761. https://doi.org/10.1210/en.2010-0792
Cannata, Dara ; Lann, Danielle ; Wu, Yingjie ; Elis, Sebastien ; Sun, Hui ; Yakar, Shoshana ; Lazzarino, Deborah A. ; Wood, Teresa L. ; LeRoith, Derek. / Elevated Circulating IGF-I Promotes Mammary Gland Development and Proliferation. In: Endocrinology. 2010 ; Vol. 151, No. 12. pp. 5751-5761.
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