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dc.contributor.authorFelice, Dana L.
dc.contributor.authorEl-Shennawy, Lamiaa
dc.contributor.authorZhao, Shuangping
dc.contributor.authorLantvit, Daniel L.
dc.contributor.authorShen, Qi
dc.contributor.authorUnterman, Terry G.
dc.contributor.authorSwanson, Steven M.
dc.contributor.authorFrasor, Jonna
dc.date.accessioned2014-03-18T02:15:42Z
dc.date.available2014-10-18T09:30:11Z
dc.date.issued2013-09
dc.identifier.bibliographicCitationFelice DL, El-Shennawy L, Zhao S, Lantvit DL, Shen Q, Unterman TG, Swanson SM, Frasor J. Growth hormone potentiates 17β-estradiol-dependent breast cancer cell proliferation independently of IGF-I receptor signaling. Endocrinology. 2013 Sep;154(9):3219-27. doi: 10.1210/en.2012-2208.en_US
dc.identifier.issn1945-7170
dc.identifier.urihttp://hdl.handle.net/10027/12825
dc.descriptionThis is a copy of an article published in the Endocrinology © 2013 Endocrine Society. The final publication is available at http://endo.endojournals.org/en_US
dc.description.abstractEstrogen 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.en_US
dc.description.sponsorshipThis 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.).en_US
dc.language.isoen_USen_US
dc.publisherEndocrine Societyen_US
dc.subjectbreast canceren_US
dc.subjectcell proliferationen_US
dc.subjectestradiolen_US
dc.subjectepidermal growth factoren_US
dc.titleGrowth Hormone Potentiates 17β-Estradiol- Dependent Breast Cancer Cell Proliferation Independently of IGF-I Receptor Signalingen_US
dc.typeArticleen_US


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