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Tissue polarity-dependent control of mammary epithelial homeostasis and cancer development: an epigenetic perspective

Sophie A Lelièvre1

  • 1Department of Basic Medical Sciences and Purdue Center for Cancer Research, Purdue University, 625 Harrison Street, Lynn Hall, West Lafayette, IN 47907-2026, USA. lelievre@purdue.edu

Journal of Mammary Gland Biology and Neoplasia
|January 27, 2010
PubMed

Insights

The apical pole, crucial for epithelial organization, influences gene expression and cell behavior through epigenetic mechanisms. Dysregulation of apical polarity proteins can promote mammary gland tumorigenesis.

Area of Science:

  • Cell Biology
  • Epigenetics
  • Tissue Polarity

Background:

  • Epithelial cells possess a defined basoapical organization, with hemidesmosomes at the basal pole and tight junctions at the apical pole.
  • Tight junctions in mammary glands separate apical and basolateral membranes, organizing signaling and cytoskeleton.
  • Apical polarity regulators and tight junction proteins impact cell phenotype and gene expression, revealing a link to the cell nucleus.

Purpose of the Study:

  • To review the role of the apical pole in epigenetic control of tissue phenotype.
  • To emphasize the importance of apical pole organization in mammary gland homeostasis and tumorigenesis.
  • To explore how apical polarity proteins influence gene expression and chromatin, impacting breast cancer.

Main Methods:

  • Literature review focusing on apical polarity regulators (Crb, Par, Scrib, Dlg, Lgl) and tight junction proteins.
  • Analysis of indirect mechanisms: signal transduction and transcription regulator localization.
  • Analysis of direct mechanisms: participation in chromatin-associated complexes.

Main Results:

  • Apical polarity proteins indirectly affect gene expression by modulating signaling pathways and transcription factor localization.
  • Apical polarity proteins directly participate in chromatin-associated complexes, influencing gene expression.
  • Alterations in the apical pole can lead to a switch in apical polarity protein function, from nuclear repressors to promoters of cancerous behavior.

Conclusions:

  • The apical pole plays a significant role in the epigenetic control of tissue phenotype.
  • Apical polarity is crucial for mammary gland homeostasis and tumorigenesis.
  • Apical polarity proteins impact breast neoplasm development through epigenetic mechanisms.

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