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From: HubMed - breast cancer <rssfwd@rssfwd.com>
Date: Sat, Jun 28, 2008 at 4:00 PM
Subject: ZIP7-mediated intracellular zinc transport contributes to aberrant growth factor signaling in anti-hormone resistant breast cancer cells.
To: mesothelioma77@gmail.com
[1]Endocrinology. 2008 Jun 26;
Taylor K, Vichova P, Jordan N, Hiscox S, Hendley R, Nicholson R
Anti-oestrogens such as Tamoxifen are the mainstay of treatment for oestrogen receptor positive breast cancer. However, their effectiveness is limited by the development of endocrine resistance, allowing tumour re-growth and progression. Importantly, in vitro MCF7 cell models of acquired tamoxifen resistance (TamR cells) display an aggressive, invasive phenotype in which activation of EGFR/IGF-1R/Src signalling plays a critical role. In this study, we report that TamR cells have increased levels of zinc and zinc transporter, ZIP7, resulting in an enhanced response to exogenous zinc which is manifested as a greatly increased growth factor receptor activation, leading to increased growth and invasion. Removal of ZIP7, using siRNA, destroys this activation of EGFR/IGF-1R/Src signalling by reducing intracellular zinc levels. Similarly it also blocks the activation of HER2, 3 and 4. This data suggests that intracellular zinc levels may be a critical factor in determining growth factor responses and that the targeting of zinc transporters may have novel therapeutic implications. We show that ZIP7 is a critical component in the redistribution of zinc from intracellular stores to the cytoplasm and, as such, is essential for the zinc-induced inhibition of phosphatases which leads to activation of growth factor receptors. Removal of ZIP7 therefore offers a means through which zinc-induced activation of growth factor receptors may be effectively suppressed and provides a mechanism of targeting multiple growth factor pathways, increasing tumour kill and preventing further development of resistance in breast cancer.
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Source: http://www.hubmed.org/display.cgi?uids=18583420
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From: HubMed - breast cancer <rssfwd@rssfwd.com>
Date: Sat, Jun 28, 2008 at 4:00 PM
Subject: ZIP7-mediated intracellular zinc transport contributes to aberrant growth factor signaling in anti-hormone resistant breast cancer cells.
To: mesothelioma77@gmail.com
[1]Endocrinology. 2008 Jun 26;
Taylor K, Vichova P, Jordan N, Hiscox S, Hendley R, Nicholson R
Anti-oestrogens such as Tamoxifen are the mainstay of treatment for oestrogen receptor positive breast cancer. However, their effectiveness is limited by the development of endocrine resistance, allowing tumour re-growth and progression. Importantly, in vitro MCF7 cell models of acquired tamoxifen resistance (TamR cells) display an aggressive, invasive phenotype in which activation of EGFR/IGF-1R/Src signalling plays a critical role. In this study, we report that TamR cells have increased levels of zinc and zinc transporter, ZIP7, resulting in an enhanced response to exogenous zinc which is manifested as a greatly increased growth factor receptor activation, leading to increased growth and invasion. Removal of ZIP7, using siRNA, destroys this activation of EGFR/IGF-1R/Src signalling by reducing intracellular zinc levels. Similarly it also blocks the activation of HER2, 3 and 4. This data suggests that intracellular zinc levels may be a critical factor in determining growth factor responses and that the targeting of zinc transporters may have novel therapeutic implications. We show that ZIP7 is a critical component in the redistribution of zinc from intracellular stores to the cytoplasm and, as such, is essential for the zinc-induced inhibition of phosphatases which leads to activation of growth factor receptors. Removal of ZIP7 therefore offers a means through which zinc-induced activation of growth factor receptors may be effectively suppressed and provides a mechanism of targeting multiple growth factor pathways, increasing tumour kill and preventing further development of resistance in breast cancer.
___
Source: http://www.hubmed.org/display.cgi?uids=18583420
--
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