Megalin‐ and Disabled‐2‐mediated uptake of vitamin D‐binding protein is modulated by all‐trans‐retinoic acid in prostate and colon epithelial cells

Abstract

Disabled‐2 (Dab2) is an adapter protein, that along with the membrane receptors megalin and cubilin, is essential for uptake of protein‐complexed 25‐hydroxycholecalciferol (25D3) in the kidney and maintenance of serum vitamin D homeostasis. Previously, we showed that mammary cells (T‐47D) also express Dab2, megalin, and cubilin and internalize vitamin D‐binding protein (DBP) by receptor‐mediated endocytosis. Moreover, induction of Dab2 and megalin by the differentiating agent all‐trans‐retinoic acid (RA) correlated with DBP uptake in mammary cells. These findings suggest that expression of Dab2, megalin, and cubilin are critical for the uptake and anti‐tumorigenic effects of vitamin D in cancer‐prone tissues. In this present study, we have extended our work by characterizing the uptake of DBP and the expression of Dab2 and megalin in prostate cancer (PC‐3 and LNCaP) and colon cancer (Caco‐2) cells. Our results indicate that Dab2 and megalin mRNA and protein are abundant in PC‐3, LNCaP, and Caco‐2 cell lines. This expression was markedly enhanced when treated with 10 μM RA. Furthermore, DBP was readily internalized by PC‐3, LNCaP, and Caco‐2 cells. Taken together, these are the first studies to our knowledge that have characterized a potential role for Dab2 and megalin in the uptake of vitamin D in prostate and colon cells. Supported by NIH SR03CA128091‐03 and Iowa State University Experiment station to MJR.