Mini review: Molecular mechanisms of immortalization of human mammary epithelial cells

David E. Wazer, Vimla Band

Research output: Contribution to journalArticle

Abstract

Normal human mammary epithelial cells (MECs) exhibit a finite life span both in vivo and in vitro. A critical event in oncogenic transformation is the ability of cells to multiply indefinitely, a phenomenon referred to as immortalization. Using human papillomavirus (HPV) oncogenes, we have recently identified multiple MEC subtypes that show distinct susceptibilities to immortalization by the HPV16 E6 and E7 oncogenes. Because HPV16 E6 and E7 inactivate two well‐known tumor suppressor proteins, p53 and Rb, respectively, these results suggest a cell‐type‐specific predominance of the tumor suppressor pathways. Indeed, E6‐ and E7‐immortalized cells exhibit dramatic reduction in the levels of p53 and Rb proteins, respectively, resulting in abrogation of p53‐ and Rb‐dependent functions, such as the cell cycle arrest response to DNA damage. Moreover, the E6‐susceptible MECs could also be immortalized by mutant p53 alone and by exposure to γ‐irradiation. Interestingly, the loss of p53 function was an early event in γ‐irradiation‐induced immortalization, further supporting the essential role of p53 in regulating the growth of these cells. Availability of these in vitro models should facilitate elucidation of the molecular mechanisms of early mammary tumorigenesis. © 1995 Wiley‐Liss, Inc.

Original languageEnglish (US)
Pages (from-to)430-434
Number of pages5
JournalRadiation Oncology Investigations
Volume3
Issue number6
DOIs
StatePublished - 1995

Keywords

  • breast cancer
  • human papillomavirus
  • immortalization
  • p53
  • retinoblastoma protein

ASJC Scopus subject areas

  • Radiological and Ultrasound Technology
  • Radiation
  • Oncology
  • Radiology Nuclear Medicine and imaging

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