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Antagonists of growth hormone-releasing hormone arrest the growth of MDA-MB-468 estrogen-independent human breast cancers in nude mice

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Abstract

Since antagonists of growth hormone-releasing hormone (GH-RH) inhibit proliferation of various tumors, in this study we investigated the effects of GH-RH antagonists MZ-5-156 or JV-1-36 on growth of estrogen-independent MDA-MB-468 human breast cancers xenografted into nude mice. Both GH-RH antagonists administered at a dose of 20 μg/day induced regression of some and growth-arrest of other tumors, while control tumors continued to grow. After 5 weeks of therapy with MZ-5-156 or JV-1-36, final volume and weight of MDA-MB-468 tumors were significantly decreased (all p values <0.001) and serum IGF-I levels as well as tumor IGF-I mRNA expression were reduced as compared with controls. High affinity binding sites for IGF-I were detected by the ligand binding method. Gene expression of human IGF-I receptors, as measured by the RT-PCR, was not significantly different in control and treated MDA-MB-468 tumors. In cell culture, IGF-I did not stimulate, GH-RH slightly stimulated, while MZ-5-156 and JV-1-36 inhibited proliferation of MDA-MB-468 cells known to possess defective insulin and IGF-I receptor signaling. The expression of mRNA for human GH-RH was found in five of 8 tumors treated with GH-RH antagonists, and in one of the five control tumors. These results suggest that GH-RH antagonists inhibit MDA-MB-468 breast cancers possibly through mechanisms involving interference with locally produced GH-RH.

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Authors and Affiliations

  1. Endocrine, Polypeptide and Cancer Institute, Veterans Affairs Medical Center, New Orleans, Louisiana, USA

    Zsuzsanna Kahán, József L. Varga, Andrew V. Schally, Zoltán Rékási, Patricia Armatis, Ioulia Chatzistamou, Tamás Czömpöly & Gábor Halmos

  2. Department of Medicine, Tulane University School of Medicine, New Orleans, Louisiana, USA

    Zsuzsanna Kahán, József L. Varga, Andrew V. Schally, Zoltán Rékási, Ioulia Chatzistamou, Tamás Czömpöly & Gábor Halmos

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  1. Zsuzsanna Kahán
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  2. Zsuzsanna Kahán
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  3. József L. Varga
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  4. József L. Varga
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  5. Andrew V. Schally
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  6. Andrew V. Schally
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  11. Ioulia Chatzistamou
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  12. Tamás Czömpöly
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Kahán, Z., Kahán, Z., Varga, J.L. et al. Antagonists of growth hormone-releasing hormone arrest the growth of MDA-MB-468 estrogen-independent human breast cancers in nude mice. Breast Cancer Res Treat 60, 71–79 (2000). https://doi.org/10.1023/A:1006363230990

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