Genetic and epigenetic changes in mammary epithelial cells may mimic early events in carcinogenesis

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

Research output: Contribution to journalArticle

66 Scopus citations

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 p16INK4a 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, 409:633-637; 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.

Original languageEnglish (US)
Pages (from-to)263-274
Number of pages12
JournalJournal of Mammary Gland Biology and Neoplasia
Volume9
Issue number3
DOIs
StatePublished - Jul 1 2004

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Keywords

  • Breast carcinogenesis
  • COX-2
  • Genomic instability
  • Human mammary epithelial cells
  • p16 hypermethylation

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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