Molecular and anatomic considerations in the pathogenesis of breast cancer

David E. Wazer, Vimla Band

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

In spite of the recent recognition of specific genes associated with an elevated lifetime incidence risk of breast cancer, the molecular mechanisms of breast tumor formation remain largely unknown. Tumorigenesis is thought to be highly complex, likely involving the accumulation of 5-10 genetic and epigenetic events. Recent investigations have begun to identify some of these events, and in vitro model systems for breast tumorigenesis, including radiation-induced breast cancer, are expected to provide further insight. Normal human breast epithelial cells 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, multiple normal breast epithelial subtypes have been shown to have distinct susceptibilities to immortalization by the HPV E6 and E7 oncogenes. Because HPV E6 and E7 inactivate two well-known tumor suppressor proteins, p53 and Rb, respectively, this suggests that a cell-type-specific predominance exists with respect to these tumor suppressor pathways. Additional evidence for variability to oncogenic stimuli among normal breast epithelial cells is provided by findings of locally confined loss of heterozygosity. An in vitro model of radiation-induced breast cancer is associated with early abrogation of p53 function. The resultant pair of normal and radiation-transformed breast epithelial cells serves as a useful system to identify other genes critically relevant to breast tumorigenesis. These and other models should help further define the molecular mechanisms underlying the early steps of breast cancer formation.

Original languageEnglish (US)
Pages (from-to)1-12
Number of pages12
JournalRadiation Oncology Investigations
Volume7
Issue number1
DOIs
StatePublished - Feb 19 1999

Fingerprint

pathogenesis
breast
Breast
cancer
Breast Neoplasms
Radiation-Induced Neoplasms
Carcinogenesis
Epithelial Cells
Oncogenes
oncogenes
Tumor Suppressor Protein p53
Loss of Heterozygosity
genes
Epigenomics
tumor suppressor proteins
Genes
radiation
tumors
suppressors
life span

Keywords

  • Breast cancer
  • Immortalization
  • Retinoblastoma protein
  • p53

ASJC Scopus subject areas

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

Cite this

Molecular and anatomic considerations in the pathogenesis of breast cancer. / Wazer, David E.; Band, Vimla.

In: Radiation Oncology Investigations, Vol. 7, No. 1, 19.02.1999, p. 1-12.

Research output: Contribution to journalArticle

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