The organizing principle: Microenvironmental influences in the normal and malignant breast

Mina J. Bissell, Derek C. Radisky, Aylin Rizki, Valerie M. Weaver, Ole W. Petersen

Research output: Contribution to journalReview article

426 Scopus citations

Abstract

The current paradigm for cancer initiation and progression rests on the groundbreaking discoveries of oncogenes and tumor suppressor genes. This framework has revealed much about the role of genetic alterations in the underlying signaling pathways central to normal cellular function and to tumor progression. However, it is clear that single gene theories or even sequential acquisition of mutations underestimate the nature of the genetic and epigenetic changes in tumors, and do not account for the observation that many cancer susceptibility genes (e.g. BRCA1, APC) show a high degree of tissue specificity in their association with neoplastic transformation. Therefore, the cellular and tissue context itself must confer additional and crucial information necessary for mutated genes to exert their influence. A considerable body of evidence now shows that cell-cell and cell-extracellular matrix (ECM) interactions are essential organizing principles that help define the nature of the tissue context, and play a crucial role in regulating homeostasis and tissue specificity. How this context determines functional integrity, and how its loss can lead to malignancy, appears to have much to do with tissue structure and polarity.

Original languageEnglish (US)
Pages (from-to)537-546
Number of pages10
JournalDifferentiation
Volume70
Issue number9-10
DOIs
StatePublished - Dec 2002

Keywords

  • 3D cultures
  • Breast cancer
  • Breast tissue
  • Luminal epithelial cells
  • Myoepithelial cells

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology
  • Cancer Research

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