Adipocyte Differentiation: Relationship to Breast Cancer

Abstract

Accumulation of adipose tissue-derived fibroblasts around malignant epithelial cells provide critical structural and biochemical support for breast carcinomas. We present evidence that this process is mediated via complex interactions between malignant epithelial cells and undifferentiated adipose tissue fibroblasts. We demonstrated that the major mechanism for fibroblast accumulation in breast tumors is the inhibition of their differentiation to mature adipocytes via the action cytokines (IL-11, TNFalpha). Malignant epithelial cells inhibit adipocyte differentiation specifically via the suppression of expression of the essential adipogenic transcription factors C/EBPalpha and PPARgamma. During this annual report period, we specifically determined the principal sources of IL-11 and TNFalpha and the distribution of expression of adipogenic transcription factors C/EBPalpha, C/EBPbeta and C/EBPdelta in sections of human breast tumors. We found that TNFalpha and IL-11 are primarily expressed in the malignant epithelial cell component of human breast tumors. Immunoreactive C/FBPalpha is not detectable in fibroblasts proximal to malignant cells, whereas in adipose tissue distant to the tumor, abundant amounts of C/EBPalpha were observed. In contrast, C/EBPbeta and C/EBPdelta are ubiquitously present in both intratumoral and distant adipose tissue fibroblasts. Thus, results obtained during this report period confirm that TNFalpha and IL-11 secreted by malignant epithelial cells block adipocyte differentiation via specifically inhibiting the expression of the essential adipogenic factor C/EBPalpha. In contrast, C/EBPbeta and C/EBPdelta levels are upregulated by malignant cells. These two latter C/EBP isoforms are not essential nor sufficient for adipocyte differentiation.

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Document Details

Document Type
Technical Report
Publication Date
Oct 01, 1999
Accession Number
ADA385810

Entities

People

  • Serdar E. Bulun

Organizations

  • University of Texas Southwestern Medical Center

Tags

DTIC Thesaurus Topics

  • Adipose Tissue
  • Biomedical Research
  • Breast Cancer
  • Cancer
  • Cell Line
  • Cells
  • Chemistry
  • Culture Media
  • Culture Techniques
  • Epithelial Cells
  • Fibroblasts
  • Inhibition
  • Molecules
  • Neoplasms
  • Proteins
  • Tissues
  • Transcription Factors

Fields of Study

  • Medicine

Readers

  • Molecular Biology and Genetics
  • Molecular and Cellular Biology
  • Oncology (Cancer Research).