CD44 expression and regulation during mammary gland development and function.

  • Hebbard L
  • Steffen A
  • Zawadzki V
 et al. 
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Abstract

The CD44v6 epitope has been widely reported to be expressed in human mammary carcinomas, yet its prognostic significance is controversial and its function in mammary tumors and mammary glands is unknown. To begin to resolve these issues, we analysed in detail the normal postnatal expression patterns and regulation of the CD44v6 epitope in murine mammary glands. We demonstrate that significant CD44v6 epitope expression is first seen during puberty, and that after puberty CD44v6 epitope expression follows the estrous cycle. CD44v6 epitope expression is observed in the myoepithelium and also less widely in luminal epithelial cells. During lactation, CD44v6 epitope expression is turned off and reappears during involution. The CD44 variant isoform bearing the v6 epitope is CD44v1-v10. Using HC11, a mammary epithelial cell line with stem cell characteristics, and facilitated by the cloning of the murine CD44 promoter, we show that growth factors and hormones which regulate ductal growth and differentiation modulate CD44 transcription. Together our data suggest that the CD44v6 epitope is expressed in mammary epithelial stems cells and in lineages derived from these cells, and that CD44v6 expression is regulated in part by hormones and growth factors such as IGF-1 and EGF which regulate the growth and differentiation of the mammary epithelium. The function of these same growth factors and hormones is often perturbed in mammary carcinomas, and we suggest that CD44v6 expression in tumors reflects this perturbation. We conclude that the expression of the CD44v6 epitope observed in some mammary tumors reflects the stem cell origin of breast tumors, and that whether or not the CD44v6 epitope is expressed in a mammary tumor is determined by the differentiation status of the tumor cells.

Author-supplied keywords

  • Animals
  • Antigens, CD44
  • Antigens, CD44: genetics
  • Antigens, CD44: metabolism
  • Base Sequence
  • Base Sequence: genetics
  • Cell Line
  • Cloning, Molecular
  • Epidermal Growth Factor
  • Epidermal Growth Factor: pharmacology
  • Epithelial Cells
  • Epithelial Cells: cytology
  • Epithelial Cells: drug effects
  • Epithelial Cells: metabolism
  • Epitopes
  • Epitopes: metabolism
  • Estrus
  • Female
  • Gene Expression Regulation, Developmental
  • Gene Expression Regulation, Developmental: genetic
  • Glycoproteins
  • Glycoproteins: genetics
  • Glycoproteins: metabolism
  • Insulin-Like Growth Factor I
  • Insulin-Like Growth Factor I: pharmacology
  • Lactation
  • Lactation: metabolism
  • Mammary Glands, Animal
  • Mammary Glands, Animal: growth & development
  • Mammary Glands, Animal: metabolism
  • Mice
  • Molecular Sequence Data
  • Pregnancy
  • Pregnancy: metabolism
  • Promoter Regions, Genetic
  • Promoter Regions, Genetic: drug effects
  • Promoter Regions, Genetic: genetics
  • Protein Isoforms
  • Protein Isoforms: drug effects
  • Protein Isoforms: genetics
  • Protein Isoforms: metabolism
  • Stem Cells
  • Stem Cells: cytology
  • Stem Cells: metabolism

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  • PMID: 10862719
  • PUI: 30599413
  • ISBN: 0021-9533
  • ISSN: 0021-9533
  • SGR: 0033887474
  • SCOPUS: 2-s2.0-0033887474

Authors

  • L Hebbard

  • a Steffen

  • V Zawadzki

  • C Fieber

  • N Howells

  • J Moll

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