Growth regulation of human colon cancer cells by epidermal growth factor and 1,25-dihydroxyvitamin D3 is mediated by mutual modulation of receptor expression

Eur J Cancer. 1998 Dec;34(13):2119-25. doi: 10.1016/s0959-8049(98)00267-6.


The human colon adenocarcinoma-derived cell line Caco-2 was used as a model system to study the interaction of epidermal growth factors (EGF) and 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) in control of colorectal cancer cell growth. The mitogenic stimulus of EGF was rapidly transduced via apical and basal membrane receptors alike into elevation of c-myc expression, causing a shift of Caco-2 cells from the G0/G1 into the S phase of the cell cycle. The stimulatory effect of EGF on cell division was effectively counteracted by 1,25(OH)2D3: the presence of the steroid hormone prevents the negative effect of EGF on vitamin D receptor abundance and concurrently minimises ligand-occupied EGF receptor numbers on both sides of Caco-2 cell monolayers. Our data suggest that EGF and 1,25-(OH)2D3 actions on mutual receptor levels represent a specific feature of the potent antimitogenic effect of the steroid hormone on colon cancer cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Northern
  • Blotting, Western
  • Caco-2 Cells / drug effects
  • Calcitriol / pharmacology*
  • Cell Division / drug effects
  • Colonic Neoplasms / metabolism
  • Colonic Neoplasms / pathology*
  • Epidermal Growth Factor / pharmacology*
  • ErbB Receptors / metabolism
  • Humans
  • Interphase / drug effects
  • Proto-Oncogene Proteins c-myc / metabolism*
  • RNA, Messenger / analysis
  • RNA, Neoplasm / analysis


  • Proto-Oncogene Proteins c-myc
  • RNA, Messenger
  • RNA, Neoplasm
  • Epidermal Growth Factor
  • ErbB Receptors
  • Calcitriol