Vitamin D Transport Proteins Megalin and disabled-2 Are Expressed in Prostate and Colon Epithelial Cells and Are Induced and Activated by All-Trans-Retinoic Acid

Nutr Cancer. 2013;65(6):900-7. doi: 10.1080/01635581.2013.805422.

Abstract

Megalin and disabled-2 (Dab2) are essential for uptake of the 25-hydroxycholecalciferol (25D3)-vitamin D binding protein (DBP) complex in tissues. In the kidney, this mechanism regulates serum 25D3 levels and production of 1,25-dihydroxycholecalciferol (1,25D3) by CYP27B1 for systemic use. Previously, we showed that mammary epithelial cells expressing CYP27B1 express megalin and Dab2 and internalize DBP by endocytosis, indicating 25D3 was accessible for conversion to 1,25D3 in extra-renal tissues. Moreover, induction of megalin and Dab2 (protein and mRNA abundance) by all-trans-retinoic acid (RA) enhanced DBP uptake. This suggests megalin and Dab2 play a central role in uptake of vitamin D and may predict actions of vitamin D in extra-renal tissues. Here, we characterized megalin and Dab2 expression and uptake of DBP in transformed human prostate and colon epithelial cells. Megalin and Dab2 were expressed in prostate and colon epithelial cells, which was markedly enhanced following treatment with RA. Furthermore, DBP uptake was stimulated by low-dose RA supplementation in LNCaP, PC-3, and Caco-2 cells. Taken together, these are the first studies to our knowledge that have demonstrated modulated expression of megalin and Dab2, as well as an association between increased expression of endocytic proteins with DBP uptake in prostate and colon cells.

Publication types

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

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Adaptor Proteins, Signal Transducing / metabolism
  • Caco-2 Cells
  • Cell Line, Tumor
  • Colon / cytology
  • Colon / drug effects
  • Colon / pathology
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Humans
  • Low Density Lipoprotein Receptor-Related Protein-2 / genetics*
  • Low Density Lipoprotein Receptor-Related Protein-2 / metabolism
  • Male
  • Prostate / cytology
  • Prostate / drug effects
  • Prostate / pathology
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Tretinoin / pharmacology
  • Tumor Suppressor Proteins / genetics*
  • Tumor Suppressor Proteins / metabolism
  • Vitamin D / pharmacokinetics*
  • Vitamin D-Binding Protein / genetics
  • Vitamin D-Binding Protein / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • DAB2 protein, human
  • Low Density Lipoprotein Receptor-Related Protein-2
  • RNA, Messenger
  • Tumor Suppressor Proteins
  • Vitamin D-Binding Protein
  • Vitamin D
  • Tretinoin