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. Previously, we showed that mammary epithelial 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 (protein and mRNA) by the differentiating agent all‐trans‐retinoic acid (RA) correlated with increased DBP uptake in mammary cells. A number of other absorptive epithelial tissues also express Dab2, which suggests that these tissues are capable of internalizing the 25D3‐DBP complex. In the present study, we examined the expression of Dab2, megalin, and cubilin in prostate epithelial (PC‐3 and LNCaP) and colon epithelial (Caco‐2) cancer cells and their ability to internalize DBP. Our preliminary results indicate that PC‐3 and Caco‐2 cells express Dab2 (mRNA and protein) and this expression was markedly enhanced when cells were treated with 10 μM RA. Taken together, these are the first studies to our knowledge that have characterized a potential role for Dab2, megalin, and cubilin in the uptake of vitamin D in prostate and colon cells. Supported by NIH 5R03CA128091‐03 and Iowa State University Experiment station to MJR.
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