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Bioactive Components of Human Milk pp 79–85Cite as

Regulation of Cell Apoptosis by Insulin-Like Growth Factor I

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Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 501))

Abstract

Correct temporal and spatial regulation of apoptosis is critical for normal mammary gland development and lactation. Previous work with a strain of trans-genic mice that overexpress des(1-3)hIGF-I during pregnancy and lactation suggested that this growth factor inhibits apoptosis. The hypothesis tested within these studies is that overexpression of des(1-3)hIGF-I within the mammary gland inhibits apoptosis and the expression of apoptosis-associated genes that are known to be activated by the transcription factor AP-1. This inhibition of apoptosis was further posited to predispose the tissue to carcinogenesis. TUNEL analysis of mammary tissue from transgenic mice that overexpress des(1-3)hIGF-I under control of the rat whey acidic protein promoter showed only 25% (P < 0.05) of the number of apoptotic cells found in nontransgenic mice at the same stage of lactation. Northern analysis of RNA from these animals showed a 75% (P = 0.08) reduction in c-Jun mRNA abundance. Histological analysis of mammary tissue from nonlactating multiparous WAP-DES mice ranging in age from 13 to 25 months showed a variety of hyper-plastic lesions. These lesions aberrantly expressed the transgene. At 23 months of age 50% of the transgenic mice within this study developed adenocarcinomas. These results support the conclusion that inhibition of apoptosis within the mammary gland by IGF-I involves decreased activity of AP-1 and predisposes the tissue to tumors.

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Authors and Affiliations

  1. USDA/ARS Children’s Nutrition Research Center Department of Pediatrics, Baylor College of Medicine, Houston, TX, 77030, USA

    Darryl L. Hadsell & Ghada Abdel-Fattah

Authors
  1. Darryl L. Hadsell
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  2. Ghada Abdel-Fattah
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Editors and Affiliations

  1. Waltham, Massachusetts and Harvard Medical School, Shriver Center, Boston, Massachusetts

    David S. Newburg

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© 2001 Springer Science+Business Media New York

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Hadsell, D.L., Abdel-Fattah, G. (2001). Regulation of Cell Apoptosis by Insulin-Like Growth Factor I. In: Newburg, D.S. (eds) Bioactive Components of Human Milk. Advances in Experimental Medicine and Biology, vol 501. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-1371-1_9

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  • DOI: https://doi.org/10.1007/978-1-4615-1371-1_9

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-5521-2

  • Online ISBN: 978-1-4615-1371-1

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