Human breast tumor slices: a model for identification of vitamin D regulated genes in the tumor microenvironment

J Steroid Biochem Mol Biol. 2010 Jul;121(1-2):151-5. doi: 10.1016/j.jsbmb.2010.03.051. Epub 2010 Mar 20.

Abstract

While many studies have addressed the direct effects of 1alpha,25(OH)2D3 on breast cancer (BC) cells, stromal-epithelial interactions, which are important for the tumor development, have been largely ignored. In addition, high concentrations of the hormone, which cannot be attained in vivo, have been used. Our aim was to establish a more physiological breast cancer model, represented by BC tissue slices, which maintain epithelial-mesenchymal interactions, cultured with a relatively low 1alpha,25(OH)2D3 concentration, in order to evaluate the vitamin D pathway. Freshly excised human BC samples were sliced and cultured in complete culture media containing vehicle, 0.5 nM or 100 nM 1alpha,25(OH)2D3 for 24 h. BC slices remained viable for at least 24 h, as evaluated by preserved tissue morphology in hematoxylin and eosin (HE) stained sections and bromodeoxyuridine (BrdU) incorporation by 10% of tumor cells. VDR mRNA expression was detected in all samples and CYP24A1 mRNA expression was induced by 1alpha,25(OH)2D3 in both concentrations (but mainly with 100 nM). Our results indicate that the vitamin D signaling pathway is functional in BC slices, a model which preserves stromal-epithelial interactions and mimics in vivo conditions.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Bromodeoxyuridine / pharmacology
  • DNA, Complementary / metabolism
  • Dose-Response Relationship, Drug
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Middle Aged
  • Models, Biological
  • Oligonucleotide Array Sequence Analysis
  • RNA, Messenger / metabolism
  • Steroid Hydroxylases / biosynthesis
  • Time Factors
  • Vitamin D / metabolism*
  • Vitamin D3 24-Hydroxylase

Substances

  • DNA, Complementary
  • RNA, Messenger
  • Vitamin D
  • Steroid Hydroxylases
  • CYP24A1 protein, human
  • Vitamin D3 24-Hydroxylase
  • Bromodeoxyuridine