The Role of BRCA1 in Suppressing Epithelial-Mesenchymal Transition in Mammary Gland and Tumor Development

Abstract

During the first year of the study, the PI has found that disrupting Brca1 by either germline or epithelium-specific mutation in p18-deficient mice activates epithelial-to-mesenchymal transition (EMT) and induces dedifferentiation of luminal stem cells (LSCs), which associate closely with expansion of basal and cancer stem cells and formation of basal-like tumors. Mechanistically, BRCA1 bound to the TWIST promoter, suppressing its activity and inhibiting EMT in mammary tumor cells. Our findings showed that BRCA1 suppressed TWIST and EMT, inhibited LSC dedifferentiation and repressed expansion of basal stem cells and basal-like tumors. Thus, our work offers the first genetic evidence that Brca1 directly suppresses EMT and LSC de-differentiation during breast tumorigenesis.

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Document Details

Document Type
Technical Report
Publication Date
Sep 01, 2014
Accession Number
ADA612714

Entities

People

  • Xin-Hai Pei

Organizations

  • University of Miami

Tags

DTIC Thesaurus Topics

  • Biomedical Research
  • Breast Cancer
  • Cancer
  • Cells
  • Epithelial Cells
  • Epithelium
  • Genes
  • Glands
  • Mammary Glands
  • Mutations
  • Neoplasms
  • Stem Cells
  • Tissues
  • Transcription Factors
  • Transitions

Fields of Study

  • Biology

Readers

  • Breast cancer cell signaling and growth regulation.
  • Immunology and Pathology
  • Molecular and genetic basis of cancer.

Technology Areas

  • Biotechnology