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Growth Hormone Potentiates 17β-Estradiol- Dependent Breast Cancer Cell Proliferation Independently of IGF-I Receptor Signaling

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posted on 18.10.2014, 00:00 authored by Dana L. Felice, Lamiaa El-Shennawy, Shuangping Zhao, Daniel L. Lantvit, Qi Shen, Terry G. Unterman, Steven M. Swanson, Jonna Frasor
Estrogen action in mammary gland development and breast cancer progression is tightly linked to the GH/IGF-I axis. Although many of the effects of GH on mammary gland growth and development require IGF-I, the extent to which GH action in breast cancer depends on IGF-I is not known. We examined GH action in a panel of estrogen receptor-positive breast cancer cell lines and found that T47D cells express significant levels of GH receptor and that GH significantly enhances 17β-estradiol (E2)-stimulated proliferation in these cells. GH action in the T47D cells was independent of changes in IGF-I and IGF-I receptor (IGF-IR) expression and IGF-IR signaling, suggesting that GH can exert direct effects on breast cancer cells. Although E2-dependent proliferation required IGF-IR signaling, the combination of GH+E2 overcame inhibition of IGF-IR activity to restore proliferation. In contrast, GH required both Janus kinase 2 and epidermal growth factor receptor signaling for subsequent ERK activation and potentiation of E2-dependent proliferation. Downstream of these pathways, we identified a number of immediate early-response genes associated with proliferation that are rapidly and robustly up-regulated by GH. These findings demonstrate that GH can have important effects in breast cancer cells that are distinct from IGF-IR activity, suggesting that novel drugs or improved combination therapies targeting estrogen receptor and the GH/IGF axis may be beneficial for breast cancer patients.

Funding

This work was supported in part by American Cancer Society Grant 119168-RSG-10-187--01-TBE (to J.F.) and National Institutes of Health Grant T32 HL07692--21 (to D.L.F.).

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Publisher Statement

This is a copy of an article published in the Endocrinology © 2013 Endocrine Society. The final publication is available at http://endo.endojournals.org/

Publisher

Endocrine Society

Language

en_US

issn

1945-7170

Issue date

01/09/2013

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