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Low pO2 and β-Estradiol Induce VEGF in MCF-7 and MCF-7-5C Cells: Relationship to in vivo Hypoxia

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Abstract

Previous work from this laboratory demonstrated that MCF-7 breast carcinoma cells grown in nude mice contained minimal hypoxia but that tamoxifen treatment of these tumors resulted in increased hypoxia (Evans S. et al., Cancer Research, 1997). These findings led to studies exploring the link between estrogen signaling and tumor oxygenation and determining the role of VEGF in this process. The stimulation of estrogen-dependent MCF-7 breast carcinoma cells in vitro with β-estradiol resulted in a two-fold induction of VEGF mRNA and 1.3–2-fold increase in protein, similar to what was observed when these cells were exposed to 0.1% oxygen. Furthermore, the two stimuli given together had an additive effect on (increasing) VEGF expression, suggesting that the combination of hypoxia and estrogen may be important in upregulating VEGF in some breast cancers. Estrogen-independent MCF-7-5C cells, developed by growing MCF-7 cells in long-term culture in estrogen-free media, were also studied. Using EF5, a fluorinated 2-nitroimidazole which localizes to hypoxic cells, MCF-7-5C tumors grown in nude mice were found to contain lower pO2 levels and more hypoxic regions than similarly grown MCF-7 tumors. We tested the hypothesis that this might be the result of defective expression of VEGF in MCF-7-5C cells in response to β-estradiol and/or hypoxia. However, MCF-7-5C and MCF-7 cells showed a similar induction of VEGF in vitro in response to either β-estradiol or hypoxia. Therefore, although these two cell lines grown as tumors have substantial differences in the presence and patterns of hypoxia, this could not be explained by a difference in VEGF induction.

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Authors and Affiliations

  1. Department of Radiation Oncology, University of Pennsylvania School of Medicine, Philadelphia, PA, 19104, USA

    Amit Maity, Walter Sall, Cameron J. Koch, Patricia R. Oprysko & Sydney M. Evans

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  1. Amit Maity
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  2. Walter Sall
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Maity, A., Sall, W., Koch, C.J. et al. Low pO2 and β-Estradiol Induce VEGF in MCF-7 and MCF-7-5C Cells: Relationship to in vivo Hypoxia. Breast Cancer Res Treat 67, 51–60 (2001). https://doi.org/10.1023/A:1010662905549

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