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Genetic and Epigenetic Changes in Mammary Epithelial Cells May Mimic Early Events in Carcinogenesis

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Abstract

Studies of human mammary epithelial cells from healthy individuals are providing novel insights into how early epigenetic and genetic events affect genomic integrity and fuel carcinogenesis. Key epigenetic changes, such as the hypermethylation of the p16 INK4a promoter sequences, create a previously unappreciated preclonal phase of tumorigenesis in which a subpopulation of mammary epithelial cells are positioned for progression to malignancy (Romanov et al., 2001, Nature, 409:633ndash;637; Tlsty et al., 2001, J. Mammary Gland Biol. Neoplasia, 6:235–243). These key changes precede the clonal outgrowth of premalignant lesions and occur frequently in healthy, disease-free women. Understanding more about these early events should provide novel molecular candidates for prevention and therapy of breast cancer that target the process instead of the consequences of genomic instability. This review will highlight some of the key alterations that have been studied in human mammary epithelial cells in culture and relate them to events observed in vivo and discussed in accompanying reviews in this volume.

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Authors and Affiliations

  1. Department of Pathology and UCSF Comprehensive Cancer Center, University of California at San Francisco, San Francisco, California

    Thea D. Tlsty, Yongping G. Crawford, Charles R. Holst, Colleen A. Fordyce, Jianmin Zhang, Kimberly McDermott, Krystyna Kozakiewicz & Mona L. Gauthier

  2. Department of Medical Oneology, Genentech Incorporation, 1 DNA Way, South San Francisco, California

    Yongping G. Crawford

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  1. Thea D. Tlsty
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  2. Yongping G. Crawford
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Tlsty, T.D., Crawford, Y.G., Holst, C.R. et al. Genetic and Epigenetic Changes in Mammary Epithelial Cells May Mimic Early Events in Carcinogenesis. J Mammary Gland Biol Neoplasia 9, 263–274 (2004). https://doi.org/10.1023/B:JOMG.0000048773.95897.5f

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